PMID-sentid	Pub_year	Sent_text	comp_official_name	comp_offset	protein_name	organism	prot_offset
33933612-6	2021	SARS-CoV-2 nsp14-nsp10 shows a metal-dependent nuclease activity but has different metal selectivity from RTC.	Metals	31-36	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	17-22
33903777-4	2021	Also, the inhibition activity of the investigated alpha-Hydrazinophosphonic acid for SARS-CoV-2 main protease (Mpro) and RNA dependent RNA polymerase (RdRp) has been predicted using in silico docking.	alpha-hydrazinophosphonic acid	50-80	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	151-155
33933612-6	2021	SARS-CoV-2 nsp14-nsp10 shows a metal-dependent nuclease activity but has different metal selectivity from RTC.	Metals	83-88	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	17-22
32338164-6	2021	The results show the effectiveness of Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine, in binding to SARS-CoV-2 RdRp.	Sofosbuvir	38-48	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	171-175
33850334-3	2021	This study aimed to identify small molecules binding to the SAM-binding site of the nsp10-nsp16 heterodimer for potential inhibition of methyltransferase activity.	S-Adenosylmethionine	60-63	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	84-89
32338164-6	2021	The results show the effectiveness of Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine, in binding to SARS-CoV-2 RdRp.	Ribavirin	50-59	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	171-175
32338164-6	2021	The results show the effectiveness of Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine, in binding to SARS-CoV-2 RdRp.	galidesivir	61-72	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	171-175
32338164-6	2021	The results show the effectiveness of Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine, in binding to SARS-CoV-2 RdRp.	remdesivir	74-84	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	171-175
32338164-6	2021	The results show the effectiveness of Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine, in binding to SARS-CoV-2 RdRp.	favipiravir	86-97	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	171-175
32338164-6	2021	The results show the effectiveness of Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine, in binding to SARS-CoV-2 RdRp.	Cefuroxime	99-109	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	171-175
32338164-6	2021	The results show the effectiveness of Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine, in binding to SARS-CoV-2 RdRp.	Tenofovir	111-120	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	171-175
32338164-6	2021	The results show the effectiveness of Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine, in binding to SARS-CoV-2 RdRp.	Hydroxychloroquine	126-144	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	171-175
33016666-3	2021	Molecular docking studies have highlighted that quercetin, a natural polyphenol belonging to the flavonol class, inhibits 3CLpro, PLpro and S proteins.	Quercetin	48-57	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	130-135
33016666-3	2021	Molecular docking studies have highlighted that quercetin, a natural polyphenol belonging to the flavonol class, inhibits 3CLpro, PLpro and S proteins.	Polyphenols	69-79	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	130-135
33016666-3	2021	Molecular docking studies have highlighted that quercetin, a natural polyphenol belonging to the flavonol class, inhibits 3CLpro, PLpro and S proteins.	3-hydroxyflavone	97-105	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	130-135
33376043-11	2021	In addition, docking simulation showed that lycorine interacts with SARS-CoV-2 RdRp at the Asp623, Asn691, and Ser759 residues through hydrogen bonding, at which the binding affinities of lycorine (-6.2 kcal/mol) were higher than those of remdesivir (-4.7 kcal/mol).	remdesivir	239-249	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	79-83
33376043-12	2021	CONCLUSIONS: Lycorine is a potent non-nucleoside direct-acting antiviral against emerging coronavirus infections and acts by inhibiting viral RdRp activity; therefore, lycorine may be a candidate against the current COVID-19 pandemic.	lycorine	13-21	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	142-146
33376043-6	2021	PURPOSE: We investigated the direct-inhibiting action of lycorine on CoV"s RdRp, as potential treatment for emerging CoV infections.	lycorine	57-65	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	75-79
33376043-12	2021	CONCLUSIONS: Lycorine is a potent non-nucleoside direct-acting antiviral against emerging coronavirus infections and acts by inhibiting viral RdRp activity; therefore, lycorine may be a candidate against the current COVID-19 pandemic.	lycorine	168-176	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	142-146
34052981-3	2021	METHODS: In the present study molecular docking technique was applied to test binding affinity of ciprofloxacin and levofloxacin-two commercially available fluoroquinolones, to SARS-CoV-2 S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLPRO).	Levofloxacin	116-128	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	272-277
34052981-0	2021	The application of in silico experimental model in the assessment of ciprofloxacin and levofloxacin interaction with main SARS-CoV-2 targets: S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLpro)-preliminary molecular docking analysis.	Ciprofloxacin	69-82	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	226-231
33423577-6	2021	In this process, we purified the nsp10-nsp16 complex to higher than 95% purity and confirmed its binding to the methyl donor SAM, the product of the reaction, S-adenosyl-l-homocysteine (SAH), and a common methyltransferase inhibitor, sinefungin, using isothermal titration calorimetry (ITC).	S-Adenosylmethionine	125-128	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	33-38
33423577-6	2021	In this process, we purified the nsp10-nsp16 complex to higher than 95% purity and confirmed its binding to the methyl donor SAM, the product of the reaction, S-adenosyl-l-homocysteine (SAH), and a common methyltransferase inhibitor, sinefungin, using isothermal titration calorimetry (ITC).	S-Adenosylhomocysteine	159-184	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	33-38
33423577-6	2021	In this process, we purified the nsp10-nsp16 complex to higher than 95% purity and confirmed its binding to the methyl donor SAM, the product of the reaction, S-adenosyl-l-homocysteine (SAH), and a common methyltransferase inhibitor, sinefungin, using isothermal titration calorimetry (ITC).	sinefungin	234-244	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	33-38
34052981-3	2021	METHODS: In the present study molecular docking technique was applied to test binding affinity of ciprofloxacin and levofloxacin-two commercially available fluoroquinolones, to SARS-CoV-2 S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLPRO).	Fluoroquinolones	156-172	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	272-277
34052981-0	2021	The application of in silico experimental model in the assessment of ciprofloxacin and levofloxacin interaction with main SARS-CoV-2 targets: S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLpro)-preliminary molecular docking analysis.	Levofloxacin	87-99	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	226-231
34052981-6	2021	In the case of TMPRSS2 protein and PLPRO protease the best docked ligand was levofloxacin and in the case of E proteins and RNA-dependent RNA polymerase the best docked ligands were levofloxacin and dexamethasone.	Levofloxacin	77-89	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	35-40
34052981-3	2021	METHODS: In the present study molecular docking technique was applied to test binding affinity of ciprofloxacin and levofloxacin-two commercially available fluoroquinolones, to SARS-CoV-2 S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLPRO).	Ciprofloxacin	98-111	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	272-277
34052981-6	2021	In the case of TMPRSS2 protein and PLPRO protease the best docked ligand was levofloxacin and in the case of E proteins and RNA-dependent RNA polymerase the best docked ligands were levofloxacin and dexamethasone.	Dexamethasone	199-212	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	35-40
34052981-7	2021	Moreover, a molecular dynamics study also reveals that ciprofloxacin and levofloxacin form a stable complex with E- and TMPRSS2 proteins, RNA polymerase and papain-like protease (PLPRO).	Ciprofloxacin	55-68	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	179-184
34052981-7	2021	Moreover, a molecular dynamics study also reveals that ciprofloxacin and levofloxacin form a stable complex with E- and TMPRSS2 proteins, RNA polymerase and papain-like protease (PLPRO).	Levofloxacin	73-85	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	179-184
33890471-0	2021	Rational Engineering of the DNA Walker Amplification Strategy by Using a Au@Ti3C2@PEI-Ru(dcbpy)32+ Nanocomposite Biosensor for Detection of the SARS-CoV-2 RdRp Gene.	Gold	73-75	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	155-159
33984267-7	2021	This conundrum is resolved by demonstrating that four HCV protease inhibitor drugs, simeprevir, vaniprevir, paritaprevir, and grazoprevir inhibit the SARS CoV-2 papain-like protease (PLpro).	Simeprevir	84-94	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	183-188
33984267-7	2021	This conundrum is resolved by demonstrating that four HCV protease inhibitor drugs, simeprevir, vaniprevir, paritaprevir, and grazoprevir inhibit the SARS CoV-2 papain-like protease (PLpro).	vaniprevir	96-106	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	183-188
33984267-7	2021	This conundrum is resolved by demonstrating that four HCV protease inhibitor drugs, simeprevir, vaniprevir, paritaprevir, and grazoprevir inhibit the SARS CoV-2 papain-like protease (PLpro).	paritaprevir	108-120	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	183-188
33984267-7	2021	This conundrum is resolved by demonstrating that four HCV protease inhibitor drugs, simeprevir, vaniprevir, paritaprevir, and grazoprevir inhibit the SARS CoV-2 papain-like protease (PLpro).	grazoprevir	126-137	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	183-188
33984267-8	2021	HCV drugs that inhibit PLpro synergize with the viral polymerase inhibitor remdesivir to inhibit virus replication, increasing remdesivir"s antiviral activity as much as 10-fold, while those that only inhibit Mpro do not synergize with remdesivir.	remdesivir	127-137	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	23-28
33984267-8	2021	HCV drugs that inhibit PLpro synergize with the viral polymerase inhibitor remdesivir to inhibit virus replication, increasing remdesivir"s antiviral activity as much as 10-fold, while those that only inhibit Mpro do not synergize with remdesivir.	remdesivir	127-137	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	23-28
33716308-3	2021	The structures of the SARS-CoV-2 and SARS-CoV PLpro in complex with interferon-stimulated gene 15 (ISG15) and lysine 48 (K48)-linked diubiquitin were utilised.	Lysine	110-116	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	46-51
33992054-3	2022	The recent clinical trials on antiviral drugs highlighted some promising compounds such as umifenovir (haemagglutinin-mediated fusion inhibitor), remdesivir (RdRp nucleoside inhibitor), and favipiravir (RdRp Inhibitor).	remdesivir	146-156	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	158-162
33992054-3	2022	The recent clinical trials on antiviral drugs highlighted some promising compounds such as umifenovir (haemagglutinin-mediated fusion inhibitor), remdesivir (RdRp nucleoside inhibitor), and favipiravir (RdRp Inhibitor).	favipiravir	190-201	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	203-207
33989635-5	2021	Here we studied the effects of the active compound NHC 5"-triphosphate (NHC-TP) against the purified SARS-CoV-2 RdRp complex.	nhc 5"-triphosphate	51-70	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	112-116
33989635-5	2021	Here we studied the effects of the active compound NHC 5"-triphosphate (NHC-TP) against the purified SARS-CoV-2 RdRp complex.	nhc-tp	72-78	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	112-116
33961167-6	2022	During docking studies, phytocompounds (ligand) 6-Hydroxyondansetron (A104) have demonstrated strong binding affinity toward receptors Mpro (PDB ID 6LU7) and PLpro (PDB ID 7JRN) with G-score of - 7.274 and - 5.672, respectively, while Quercitrin (A166) also showed strong binding affinity toward ADRP (PDB ID 6W02) with G-score -6.788.	6-Hydroxy Ondansetron	48-68	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	158-163
33961167-6	2022	During docking studies, phytocompounds (ligand) 6-Hydroxyondansetron (A104) have demonstrated strong binding affinity toward receptors Mpro (PDB ID 6LU7) and PLpro (PDB ID 7JRN) with G-score of - 7.274 and - 5.672, respectively, while Quercitrin (A166) also showed strong binding affinity toward ADRP (PDB ID 6W02) with G-score -6.788.	quercitrin	235-245	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	158-163
33961167-8	2022	The ADME-Tox study performed using SwissADMEserver for pharmacokinetics of the selected phytocompounds 6-Hydroxyondansetron (A104) and Quercitrin (A166) demonstrated that 6-Hydroxyondansetron passes all the required drug discovery rules which can potentially inhibit Mpro and PLpro of SARS-CoV-2 without causing toxicity while Quercitrin demonstrated less drug-like properties but also demonstrated as potential inhibitor for ADRP.	adme	4-8	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	276-281
33961167-8	2022	The ADME-Tox study performed using SwissADMEserver for pharmacokinetics of the selected phytocompounds 6-Hydroxyondansetron (A104) and Quercitrin (A166) demonstrated that 6-Hydroxyondansetron passes all the required drug discovery rules which can potentially inhibit Mpro and PLpro of SARS-CoV-2 without causing toxicity while Quercitrin demonstrated less drug-like properties but also demonstrated as potential inhibitor for ADRP.	6-Hydroxy Ondansetron	103-123	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	276-281
33961167-8	2022	The ADME-Tox study performed using SwissADMEserver for pharmacokinetics of the selected phytocompounds 6-Hydroxyondansetron (A104) and Quercitrin (A166) demonstrated that 6-Hydroxyondansetron passes all the required drug discovery rules which can potentially inhibit Mpro and PLpro of SARS-CoV-2 without causing toxicity while Quercitrin demonstrated less drug-like properties but also demonstrated as potential inhibitor for ADRP.	quercitrin	135-145	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	276-281
33961167-8	2022	The ADME-Tox study performed using SwissADMEserver for pharmacokinetics of the selected phytocompounds 6-Hydroxyondansetron (A104) and Quercitrin (A166) demonstrated that 6-Hydroxyondansetron passes all the required drug discovery rules which can potentially inhibit Mpro and PLpro of SARS-CoV-2 without causing toxicity while Quercitrin demonstrated less drug-like properties but also demonstrated as potential inhibitor for ADRP.	6-Hydroxy Ondansetron	171-191	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	276-281
33961167-8	2022	The ADME-Tox study performed using SwissADMEserver for pharmacokinetics of the selected phytocompounds 6-Hydroxyondansetron (A104) and Quercitrin (A166) demonstrated that 6-Hydroxyondansetron passes all the required drug discovery rules which can potentially inhibit Mpro and PLpro of SARS-CoV-2 without causing toxicity while Quercitrin demonstrated less drug-like properties but also demonstrated as potential inhibitor for ADRP.	quercitrin	327-337	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	276-281
34038639-0	2021	Quinoline and Quinazoline Derivatives Inhibit Viral RNA Synthesis by SARS-CoV-2 RdRp.	quinoline	0-9	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	80-84
34038639-0	2021	Quinoline and Quinazoline Derivatives Inhibit Viral RNA Synthesis by SARS-CoV-2 RdRp.	Quinazolines	14-25	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	80-84
34038639-4	2021	In this study, 101 quinoline and quinazoline derivatives were screened against SARS-CoV-2 RdRp using a cell-based assay.	quinoline	19-28	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-94
34038639-4	2021	In this study, 101 quinoline and quinazoline derivatives were screened against SARS-CoV-2 RdRp using a cell-based assay.	Quinazolines	33-44	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-94
34038639-5	2021	Three compounds I-13e, I-13h, and I-13i exhibit remarkable potency in inhibiting RNA synthesis driven by SARS-CoV-2 RdRp and relatively low cytotoxicity.	i-13e	16-21	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	116-120
34038639-5	2021	Three compounds I-13e, I-13h, and I-13i exhibit remarkable potency in inhibiting RNA synthesis driven by SARS-CoV-2 RdRp and relatively low cytotoxicity.	i-13h	23-28	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	116-120
34038639-5	2021	Three compounds I-13e, I-13h, and I-13i exhibit remarkable potency in inhibiting RNA synthesis driven by SARS-CoV-2 RdRp and relatively low cytotoxicity.	i-13i	34-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	116-120
34038639-6	2021	Among these three compounds, I-13e showed the strongest inhibition upon RNA synthesis driven by SARS-CoV-2 RdRp, the resistance to viral exoribonuclease activity and the inhibitory effect on the replication of CoV, thus holding potential of being drug candidate for treatment of SARS-CoV-2.	i-13e	29-34	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	107-111
33972410-2	2021	These modifications are performed by the Nsp10/14 and Nsp10/16 heterodimers using S-adenosylmethionine as the methyl donor.	S-Adenosylmethionine	82-102	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	41-49
33972410-2	2021	These modifications are performed by the Nsp10/14 and Nsp10/16 heterodimers using S-adenosylmethionine as the methyl donor.	S-Adenosylmethionine	82-102	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	54-62
33972410-3	2021	Nsp10/16 heterodimer is responsible for the methylation at the ribose 2"-O position of the first nucleotide.	Ribose	63-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	0-8
34008129-8	2022	Caesalpiniaphenol A not only possess a double ring aromatic moiety but also has lowest minimum binding energy, which is at par with the control GRL0617, the only known inhibitor of SARS-CoV2 PLpro.	caesalpiniaphenol	0-17	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	191-196
34008129-9	2022	Details of the Molecular Dynamics (MD) simulation and ADMET analysis helped to conclusively determine Caesalpiniaphenol A as potentially an inhibitor of SARS-CoV2 PLpro.	caesalpiniaphenol	102-119	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	163-168
33984041-6	2021	Hydrogen bonding, salt-bridge and water mediated interactions supported by MM-GBSA free energy of binding revealed strong binding of cordifolide A and sitoindoside IX to RdRP.	Hydrogen	0-8	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	170-174
33984041-6	2021	Hydrogen bonding, salt-bridge and water mediated interactions supported by MM-GBSA free energy of binding revealed strong binding of cordifolide A and sitoindoside IX to RdRP.	Water	34-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	170-174
33984041-6	2021	Hydrogen bonding, salt-bridge and water mediated interactions supported by MM-GBSA free energy of binding revealed strong binding of cordifolide A and sitoindoside IX to RdRP.	cordifolide	133-144	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	170-174
33984041-6	2021	Hydrogen bonding, salt-bridge and water mediated interactions supported by MM-GBSA free energy of binding revealed strong binding of cordifolide A and sitoindoside IX to RdRP.	sitoindoside	151-163	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	170-174
33883267-5	2021	The results establish that the single-stranded 3" segment of the product RNA generated by backtracking extrudes through the RdRp nucleoside triphosphate (NTP) entry tunnel, that a mismatched nucleotide at the product RNA 3" end frays and enters the NTP entry tunnel to initiate backtracking, and that nsp13 stimulates RdRp backtracking.	[[(2R,3S,4R,5S)-3,4-dihydroxy-5-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	129-152	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	124-128
33883267-5	2021	The results establish that the single-stranded 3" segment of the product RNA generated by backtracking extrudes through the RdRp nucleoside triphosphate (NTP) entry tunnel, that a mismatched nucleotide at the product RNA 3" end frays and enters the NTP entry tunnel to initiate backtracking, and that nsp13 stimulates RdRp backtracking.	[[(2R,3S,4R,5S)-3,4-dihydroxy-5-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	129-152	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	318-322
33883267-5	2021	The results establish that the single-stranded 3" segment of the product RNA generated by backtracking extrudes through the RdRp nucleoside triphosphate (NTP) entry tunnel, that a mismatched nucleotide at the product RNA 3" end frays and enters the NTP entry tunnel to initiate backtracking, and that nsp13 stimulates RdRp backtracking.	ntp	154-157	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	124-128
33883267-5	2021	The results establish that the single-stranded 3" segment of the product RNA generated by backtracking extrudes through the RdRp nucleoside triphosphate (NTP) entry tunnel, that a mismatched nucleotide at the product RNA 3" end frays and enters the NTP entry tunnel to initiate backtracking, and that nsp13 stimulates RdRp backtracking.	ntp	154-157	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	318-322
33883267-5	2021	The results establish that the single-stranded 3" segment of the product RNA generated by backtracking extrudes through the RdRp nucleoside triphosphate (NTP) entry tunnel, that a mismatched nucleotide at the product RNA 3" end frays and enters the NTP entry tunnel to initiate backtracking, and that nsp13 stimulates RdRp backtracking.	ntp	249-252	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	124-128
33890471-0	2021	Rational Engineering of the DNA Walker Amplification Strategy by Using a Au@Ti3C2@PEI-Ru(dcbpy)32+ Nanocomposite Biosensor for Detection of the SARS-CoV-2 RdRp Gene.	pei-ru(dcbpy)	82-95	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	155-159
33841878-1	2021	Background: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV2) depends on RNA-dependent RNA polymerase (RdRp) enzyme complex for its genomic replications and thus can be inhibited by nucleoside analogues.	Nucleosides	192-202	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	113-117
33841878-2	2021	An example is Remdesivir, which is a non-obligate chain terminator of RdRp.	remdesivir	14-24	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	70-74
33556871-4	2021	The present article provides an overview of these small-molecule therapeutics based on insights from medicinal chemistry research and focuses on RNA-dependent RNA polymerase (RdRp) inhibitors, such as the nucleoside analogues remdesivir, favipiravir and ribavirin.	Nucleosides	205-215	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	175-179
33459817-0	2021	Addressing the potential role of curcumin in the prevention of COVID-19 by targeting the Nsp9 replicase protein through molecular docking.	Curcumin	33-41	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	89-93
33459817-5	2021	The in silico molecular docking of curcumin with the replicase enzyme gave insights into the preventive measures against the virus as curcumin showed multiple interactions with Nsp9 replicase.	Curcumin	35-43	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	177-181
33459817-5	2021	The in silico molecular docking of curcumin with the replicase enzyme gave insights into the preventive measures against the virus as curcumin showed multiple interactions with Nsp9 replicase.	Curcumin	134-142	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	177-181
33556871-4	2021	The present article provides an overview of these small-molecule therapeutics based on insights from medicinal chemistry research and focuses on RNA-dependent RNA polymerase (RdRp) inhibitors, such as the nucleoside analogues remdesivir, favipiravir and ribavirin.	remdesivir	226-236	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	175-179
33556871-4	2021	The present article provides an overview of these small-molecule therapeutics based on insights from medicinal chemistry research and focuses on RNA-dependent RNA polymerase (RdRp) inhibitors, such as the nucleoside analogues remdesivir, favipiravir and ribavirin.	favipiravir	238-249	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	175-179
33556871-4	2021	The present article provides an overview of these small-molecule therapeutics based on insights from medicinal chemistry research and focuses on RNA-dependent RNA polymerase (RdRp) inhibitors, such as the nucleoside analogues remdesivir, favipiravir and ribavirin.	Ribavirin	254-263	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	175-179
33561649-8	2021	Finally, the binding affinities of all the compounds were also compared with a reference ligand, remdesivir, against the target protein RdRp.	remdesivir	97-107	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	136-140
33760271-11	2021	The molecular docking binding energies of the six index components of Liupao tea with SARS-CoV-2 3CLpro were all less than -5.0 kJ/mol, among them, the enzyme activity experiment shows that EGCG has a certain inhibitory effect on SARS-CoV-2 3CLpro , it can be used as a potential SARS-CoV-2 3CLpro inhibitor.	epigallocatechin gallate	190-194	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	241-247
33561649-11	2021	In contrast, gingerol has shown strong interactions with spike protein, and RdRp and quercetin with main protease (Mpro) of SARS-CoV-2.	gingerol	13-21	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	76-80
33760271-11	2021	The molecular docking binding energies of the six index components of Liupao tea with SARS-CoV-2 3CLpro were all less than -5.0 kJ/mol, among them, the enzyme activity experiment shows that EGCG has a certain inhibitory effect on SARS-CoV-2 3CLpro , it can be used as a potential SARS-CoV-2 3CLpro inhibitor.	epigallocatechin gallate	190-194	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	241-247
33711743-7	2021	RESULTS: The results indicated that idarubicin (IDR), a member of the anthracycline antibiotic family, and fenoterol (FNT), a known beta-2 adrenergic agonist drug, tightly bind to the target enzyme and could be used as potential anti-RdRP inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).	Idarubicin	36-46	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	234-238
33711743-7	2021	RESULTS: The results indicated that idarubicin (IDR), a member of the anthracycline antibiotic family, and fenoterol (FNT), a known beta-2 adrenergic agonist drug, tightly bind to the target enzyme and could be used as potential anti-RdRP inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).	Anthracyclines	70-83	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	234-238
33711743-7	2021	RESULTS: The results indicated that idarubicin (IDR), a member of the anthracycline antibiotic family, and fenoterol (FNT), a known beta-2 adrenergic agonist drug, tightly bind to the target enzyme and could be used as potential anti-RdRP inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).	Fenoterol	107-116	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	234-238
33760271-0	2021	Study on the mechanism of active components of Liupao tea on 3CLpro based on HPLC-DAD fingerprint and molecular docking technique.	liupao tea	47-57	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	61-67
33760271-8	2021	The results of in vitro activity showed that the IC50 of EGCG was 8.84 mumol/L, which could inhibit SARS-CoV-2 3Clpro to a certain extent.	epigallocatechin gallate	57-61	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-117
33760271-9	2021	This study unleashed that EGCG has a certain inhibitory effect on SARS-CoV-2 3CLpro , and Liupao tea has a certain significance as a tea drink for the prevention of COVID-19.	epigallocatechin gallate	26-30	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	77-83
33760271-11	2021	The molecular docking binding energies of the six index components of Liupao tea with SARS-CoV-2 3CLpro were all less than -5.0 kJ/mol, among them, the enzyme activity experiment shows that EGCG has a certain inhibitory effect on SARS-CoV-2 3CLpro , it can be used as a potential SARS-CoV-2 3CLpro inhibitor.	epigallocatechin gallate	190-194	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	97-103
33887223-7	2021	Further computational molecular investigation revealed that Taroxaz-104 molecule strongly inhibits one of the potential active sites of nCoV-RdRp (the one with which GS-443902 molecule mainly interacts), since it interacts with at least seven major active amino acid residues of its predicted pocket.	taroxaz	60-67	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	141-145
33556646-11	2021	Our findings indicate that hypericin possessed inhibition activity, and both rutin and cyanidin-3-O-glucoside resulted in a concentration-dependent inhibition of the PLpro, with activity in the micromolar range.	hypericin	27-36	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	166-171
33556646-11	2021	Our findings indicate that hypericin possessed inhibition activity, and both rutin and cyanidin-3-O-glucoside resulted in a concentration-dependent inhibition of the PLpro, with activity in the micromolar range.	Rutin	77-82	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	166-171
33556646-11	2021	Our findings indicate that hypericin possessed inhibition activity, and both rutin and cyanidin-3-O-glucoside resulted in a concentration-dependent inhibition of the PLpro, with activity in the micromolar range.	cyanidin-3-o-glucoside	87-109	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	166-171
33948598-0	2021	Allosteric activation of SARS-CoV-2 RdRp by remdesivir triphosphate and other phosphorylated nucleotides.	remdesivir	44-54	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	36-40
33948598-1	2021	The catalytic subunit of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), Nsp12, has a unique NiRAN domain that transfers nucleoside monophosphates to the Nsp9 protein.	Parathion	93-98	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	66-70
33948598-1	2021	The catalytic subunit of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), Nsp12, has a unique NiRAN domain that transfers nucleoside monophosphates to the Nsp9 protein.	Parathion	93-98	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	154-158
33948598-1	2021	The catalytic subunit of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), Nsp12, has a unique NiRAN domain that transfers nucleoside monophosphates to the Nsp9 protein.	nucleoside monophosphates	121-146	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	66-70
33948598-1	2021	The catalytic subunit of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), Nsp12, has a unique NiRAN domain that transfers nucleoside monophosphates to the Nsp9 protein.	nucleoside monophosphates	121-146	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	154-158
33948598-6	2021	Highlights: Codon-optimization of Nsp12 triggers misfolding and activity lossSlow translation, accessory Nsp7 and Nsp8 subunits, and NTPs rescue Nsp12Non-substrate nucleotides activate RNA chain synthesis, likely via NiRAN domainCrosstalk between two Nsp12 active sites that bind the same ligands.	nsp12non	145-153	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	105-109
33948598-6	2021	Highlights: Codon-optimization of Nsp12 triggers misfolding and activity lossSlow translation, accessory Nsp7 and Nsp8 subunits, and NTPs rescue Nsp12Non-substrate nucleotides activate RNA chain synthesis, likely via NiRAN domainCrosstalk between two Nsp12 active sites that bind the same ligands.	nsp12non	145-153	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	114-118
33894278-3	2021	However, the cell-free SARS-CoV-2 RdRp biochemical assay requires the conversion of nucleotide prodrugs into the active triphosphate forms, which regularly occurs in cells yet is a complicated multiple-step chemical process in vitro, and thus hinders the utility of this cell-free assay in the rapid discovery of RdRp inhibitors.	triphosphoric acid	120-132	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	34-38
33894278-3	2021	However, the cell-free SARS-CoV-2 RdRp biochemical assay requires the conversion of nucleotide prodrugs into the active triphosphate forms, which regularly occurs in cells yet is a complicated multiple-step chemical process in vitro, and thus hinders the utility of this cell-free assay in the rapid discovery of RdRp inhibitors.	triphosphoric acid	120-132	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	313-317
33894278-6	2021	By testing seven commonly used nucleotide analog viral polymerase inhibitors, Remdesivir, Molnupiravir, Ribavirin, Favipiravir, Penciclovir, Entecavir and Tenofovir, we found that both Molnupiravir and Remdesivir showed the strong inhibition of SARS-CoV-2 RdRp, with EC50 value of 0.22 muM and 0.67 muM, respectively.	Tenofovir	155-164	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	256-260
33894278-6	2021	By testing seven commonly used nucleotide analog viral polymerase inhibitors, Remdesivir, Molnupiravir, Ribavirin, Favipiravir, Penciclovir, Entecavir and Tenofovir, we found that both Molnupiravir and Remdesivir showed the strong inhibition of SARS-CoV-2 RdRp, with EC50 value of 0.22 muM and 0.67 muM, respectively.	EIDD 2801	185-197	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	256-260
33887223-7	2021	Further computational molecular investigation revealed that Taroxaz-104 molecule strongly inhibits one of the potential active sites of nCoV-RdRp (the one with which GS-443902 molecule mainly interacts), since it interacts with at least seven major active amino acid residues of its predicted pocket.	Remdesivir triphosphate	166-175	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	141-145
33864621-6	2021	Here we discovered four compounds, YM155, cryptotanshinone, tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 mumol/L.	cryptotanshinone	42-58	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	109-114
33864621-6	2021	Here we discovered four compounds, YM155, cryptotanshinone, tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 mumol/L.	tanshinone	48-58	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	109-114
33898520-0	2021	Structure-Based Virtual Screening to Identify Novel Potential Compound as an Alternative to Remdesivir to Overcome the RdRp Protein Mutations in SARS-CoV-2.	remdesivir	92-102	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	119-123
33898520-8	2021	In this study, we aimed to determine the potency of lead compounds similar to Remdesivir, which can be used as an alternative when variants of SARS-CoV-2 develop resistance due to RdRp mutations.	remdesivir	78-88	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	180-184
33898520-11	2021	These seven compounds were further analyzed for their molecular interactions, which revealed that all seven compounds interacted with RdRp with higher affinity than Remdesivir under native conditions.	remdesivir	165-175	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	134-138
33842191-8	2021	These studies suggested that bromocriptine can be the best candidate for TMPRSS2, Main protease, and RdRp protein.	Bromocriptine	29-42	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	101-105
33842675-6	2021	All the phytochemicals follow Lipinski"s rule of five and molecular docking result shows best binding affinity of Podofilox - 7.54 kcal/mol with ACE2, Psoralidin - 8.04 kcal/mol with Furin, Ursolic acid - 8.88 kcal/mol with 3CLpro and Epiafzelechin - 8.26 kcal/mol with RdRp.	Podophyllotoxin	114-123	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	270-274
33159807-0	2021	1H, 13C, and 15N backbone chemical shift assignments of coronavirus-2 non-structural protein Nsp10.	Hydrogen	0-2	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	93-98
33842675-6	2021	All the phytochemicals follow Lipinski"s rule of five and molecular docking result shows best binding affinity of Podofilox - 7.54 kcal/mol with ACE2, Psoralidin - 8.04 kcal/mol with Furin, Ursolic acid - 8.88 kcal/mol with 3CLpro and Epiafzelechin - 8.26 kcal/mol with RdRp.	psoralidin	151-161	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	270-274
33842675-8	2021	Also blocking viral proteins 3CLpro and RdRp with Ursolic acid and Epiafzelechin may prevent viral replication or transcription.	ursolic acid	50-62	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	40-44
33842675-8	2021	Also blocking viral proteins 3CLpro and RdRp with Ursolic acid and Epiafzelechin may prevent viral replication or transcription.	epiafzelechin	67-80	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	40-44
33219414-8	2021	We here report the near-complete NMR backbone and sidechain resonance assignment (1H,13C,15N) of isolated nsp7 from SARS-CoV-2 in solution.	Hydrogen	82-84	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	106-110
33159807-0	2021	1H, 13C, and 15N backbone chemical shift assignments of coronavirus-2 non-structural protein Nsp10.	15n	13-16	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	93-98
33219414-8	2021	We here report the near-complete NMR backbone and sidechain resonance assignment (1H,13C,15N) of isolated nsp7 from SARS-CoV-2 in solution.	Carbon-13	85-88	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	106-110
33655751-2	2021	Nucleoside analogs such as Remdesivir and beta-d-N4-hydroxycytidine are antiviral candidates and may function as chain terminators or induce viral mutations, thus impairing RdRp function.	Nucleosides	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	173-177
33219414-8	2021	We here report the near-complete NMR backbone and sidechain resonance assignment (1H,13C,15N) of isolated nsp7 from SARS-CoV-2 in solution.	15n	89-92	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	106-110
33392924-2	2021	To capture insights into the dynamics of the protein"s backbone in solution and accelerate the identification and mapping of ligand-binding surfaces through chemical shift perturbation studies, the backbone 1H, 13C, and 15N NMR chemical shifts for Nsp9 have been extensively assigned.	Hydrogen	207-209	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	248-252
33392924-2	2021	To capture insights into the dynamics of the protein"s backbone in solution and accelerate the identification and mapping of ligand-binding surfaces through chemical shift perturbation studies, the backbone 1H, 13C, and 15N NMR chemical shifts for Nsp9 have been extensively assigned.	15n	220-223	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	248-252
33392924-4	2021	A major feature of the assignments was the "missing" amide resonances for N96-L106 in the 1H-15N HSQC spectrum, a region that comprises almost the complete C-terminal alpha-helix that forms a major part of the homodimer interface in the crystal structure of SARS-CoV-2 Nsp9, suggesting this region either undergoes intermediate motion in the ms to mus timescale and/or is heterogenous.	n96	74-77	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	269-273
33392924-4	2021	A major feature of the assignments was the "missing" amide resonances for N96-L106 in the 1H-15N HSQC spectrum, a region that comprises almost the complete C-terminal alpha-helix that forms a major part of the homodimer interface in the crystal structure of SARS-CoV-2 Nsp9, suggesting this region either undergoes intermediate motion in the ms to mus timescale and/or is heterogenous.	Ketoisophorone	78-82	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	269-273
33392924-4	2021	A major feature of the assignments was the "missing" amide resonances for N96-L106 in the 1H-15N HSQC spectrum, a region that comprises almost the complete C-terminal alpha-helix that forms a major part of the homodimer interface in the crystal structure of SARS-CoV-2 Nsp9, suggesting this region either undergoes intermediate motion in the ms to mus timescale and/or is heterogenous.	Hydrogen	90-92	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	269-273
33662683-8	2021	For instance, three drugs Benserazide, Dobutamine and Masoprocol showed a superior consensus enrichment against the PLpro conformations.	Benserazide	26-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	116-121
33662683-8	2021	For instance, three drugs Benserazide, Dobutamine and Masoprocol showed a superior consensus enrichment against the PLpro conformations.	Dobutamine	39-49	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	116-121
33662683-8	2021	For instance, three drugs Benserazide, Dobutamine and Masoprocol showed a superior consensus enrichment against the PLpro conformations.	Masoprocol	54-64	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	116-121
33662683-9	2021	Further MD simulations for these drugs complexed with PLpro suggested the superior stability and binding of dobutamine and masoprocol inside the binding site compared to Benserazide.	Dobutamine	108-118	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	54-59
33662683-9	2021	Further MD simulations for these drugs complexed with PLpro suggested the superior stability and binding of dobutamine and masoprocol inside the binding site compared to Benserazide.	Masoprocol	123-133	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	54-59
33662683-9	2021	Further MD simulations for these drugs complexed with PLpro suggested the superior stability and binding of dobutamine and masoprocol inside the binding site compared to Benserazide.	Benserazide	170-181	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	54-59
33607929-6	2021	Critical Issues: Combining H2S physiology and currently available knowledge of COVID-19, H2S is hypothesized to target three main vulnerabilities of SARS-CoV-2: 1) cell entry through interfering with functional host receptors, 2) viral replication through acting on RNA-dependent RNA-polymerase (RdRp), and 3) the escalation of inflammation to a potentially lethal hyperinflammatory cytokine storm (TLR4 pathway and NLRP3 inflammasome).	Deuterium	27-30	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	296-300
33607929-6	2021	Critical Issues: Combining H2S physiology and currently available knowledge of COVID-19, H2S is hypothesized to target three main vulnerabilities of SARS-CoV-2: 1) cell entry through interfering with functional host receptors, 2) viral replication through acting on RNA-dependent RNA-polymerase (RdRp), and 3) the escalation of inflammation to a potentially lethal hyperinflammatory cytokine storm (TLR4 pathway and NLRP3 inflammasome).	Deuterium	89-92	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	296-300
33757133-6	2021	RESULTS: We found a total of 32 studies, out of which only 14 were relevant and were included in our review.Molecular computational studies showed that famotidine selectively acts on viral replication proteases papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro).	Famotidine	152-162	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	233-238
33655751-2	2021	Nucleoside analogs such as Remdesivir and beta-d-N4-hydroxycytidine are antiviral candidates and may function as chain terminators or induce viral mutations, thus impairing RdRp function.	remdesivir	27-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	173-177
33655751-2	2021	Nucleoside analogs such as Remdesivir and beta-d-N4-hydroxycytidine are antiviral candidates and may function as chain terminators or induce viral mutations, thus impairing RdRp function.	N(4)-hydroxycytidine	42-67	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	173-177
33655751-3	2021	Recently disclosed Cryo-EM structures of apo, RNA-bound, and inhibitor-bound SARS-CoV-2 RdRp provided insight into the inhibitor-bound structure by capturing the enzyme with its reaction product: Remdesivir covalently bound to the RNA primer strand.	remdesivir	196-206	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	88-92
33655751-4	2021	To gain a structural understanding of the binding of this and several other nucleoside analogs in the precatalytic state, molecular models were developed that predict the noncovalent interactions to a complex of SARS-CoV-2 RdRp, RNA, and catalytic metal cations.	Nucleosides	76-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	223-227
33518774-2	2021	The results of the present investigation show that ellagic acid and apigenin possess the highest binding affinities of -7.1 and -6.5 Kcal.mol-1against nsp9 and -6.9 and -7.1 Kcal.mol-1 against nsp10, respectively.	Ellagic Acid	51-63	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	151-173
33734021-8	2021	The ARVs predicted to bind the catalytic site of the RdRp included Nucleoside Reverse Transcriptase Inhibitors, abacavir, emtricitabine, zidovudine, and tenofovir.	abacavir	112-120	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	53-57
33734021-8	2021	The ARVs predicted to bind the catalytic site of the RdRp included Nucleoside Reverse Transcriptase Inhibitors, abacavir, emtricitabine, zidovudine, and tenofovir.	Emtricitabine	122-135	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	53-57
33734021-8	2021	The ARVs predicted to bind the catalytic site of the RdRp included Nucleoside Reverse Transcriptase Inhibitors, abacavir, emtricitabine, zidovudine, and tenofovir.	Zidovudine	137-147	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	53-57
33734021-8	2021	The ARVs predicted to bind the catalytic site of the RdRp included Nucleoside Reverse Transcriptase Inhibitors, abacavir, emtricitabine, zidovudine, and tenofovir.	Tenofovir	153-162	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	53-57
33518774-2	2021	The results of the present investigation show that ellagic acid and apigenin possess the highest binding affinities of -7.1 and -6.5 Kcal.mol-1against nsp9 and -6.9 and -7.1 Kcal.mol-1 against nsp10, respectively.	Ellagic Acid	51-63	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	193-198
33518774-2	2021	The results of the present investigation show that ellagic acid and apigenin possess the highest binding affinities of -7.1 and -6.5 Kcal.mol-1against nsp9 and -6.9 and -7.1 Kcal.mol-1 against nsp10, respectively.	Apigenin	68-76	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	151-173
33518774-2	2021	The results of the present investigation show that ellagic acid and apigenin possess the highest binding affinities of -7.1 and -6.5 Kcal.mol-1against nsp9 and -6.9 and -7.1 Kcal.mol-1 against nsp10, respectively.	Apigenin	68-76	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	193-198
33758867-8	2021	The SARS-CoV-2 genome is replicated and transcribed by its RNA-dependent RNA polymerase (RdRp), which is the target for antivirals such as remdesivir.	remdesivir	139-149	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	89-93
33688867-3	2021	It supersedes other NTP analogues because it not only terminates the polymerization activity of RNA-dependent RNA polymerase (RdRp), but also inhibits the proofreading activity of intrinsic exoribonuclease (ExoN).	ntp	20-23	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-130
33688867-4	2021	Even though the static structure of Remdesivir binding to RdRp has been solved and biochemical experiments have suggested it to be a "delayed chain terminator", the underlying molecular mechanisms is not fully understood.	remdesivir	36-46	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	58-62
33688867-6	2021	We found that when Remdesivir locates at an upstream site in RdRp, the 1"-cyano group experiences electrostatic interactions with a salt bridge (Asp865-Lys593), which subsequently halts translocation.	remdesivir	19-29	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	61-65
33715595-5	2021	Among the 70 tea bioactives screened, theaflavin 3,3"-di-gallate (TF3), Procyanidin B2 and Theaflavin 3-gallate (TF2a) exhibited highest binding affinities towards RdRp, 3CLpro/Mpro and PLpro targets of SARS-CoV-2 with low docking scores of -14.92, -11.68 and -10.90 kcal/mol, respectively.	theaflavin-3,3'-digallate	38-64	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	164-168
33715595-5	2021	Among the 70 tea bioactives screened, theaflavin 3,3"-di-gallate (TF3), Procyanidin B2 and Theaflavin 3-gallate (TF2a) exhibited highest binding affinities towards RdRp, 3CLpro/Mpro and PLpro targets of SARS-CoV-2 with low docking scores of -14.92, -11.68 and -10.90 kcal/mol, respectively.	theaflavin-3,3'-digallate	38-64	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	186-191
33694010-9	2021	PAMAM-functionalized SiQDs were used as a versatile electrochemical platform for the SARS-CoV-2 RdRP detection based on a signal off sensing strategy.	pamam	0-5	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	96-100
33715595-5	2021	Among the 70 tea bioactives screened, theaflavin 3,3"-di-gallate (TF3), Procyanidin B2 and Theaflavin 3-gallate (TF2a) exhibited highest binding affinities towards RdRp, 3CLpro/Mpro and PLpro targets of SARS-CoV-2 with low docking scores of -14.92, -11.68 and -10.90 kcal/mol, respectively.	theaflavin-3,3'-digallate	66-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	164-168
33715595-5	2021	Among the 70 tea bioactives screened, theaflavin 3,3"-di-gallate (TF3), Procyanidin B2 and Theaflavin 3-gallate (TF2a) exhibited highest binding affinities towards RdRp, 3CLpro/Mpro and PLpro targets of SARS-CoV-2 with low docking scores of -14.92, -11.68 and -10.90 kcal/mol, respectively.	theaflavin-3,3'-digallate	66-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	186-191
33715595-5	2021	Among the 70 tea bioactives screened, theaflavin 3,3"-di-gallate (TF3), Procyanidin B2 and Theaflavin 3-gallate (TF2a) exhibited highest binding affinities towards RdRp, 3CLpro/Mpro and PLpro targets of SARS-CoV-2 with low docking scores of -14.92, -11.68 and -10.90 kcal/mol, respectively.	procyanidin B2	72-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	164-168
33715595-5	2021	Among the 70 tea bioactives screened, theaflavin 3,3"-di-gallate (TF3), Procyanidin B2 and Theaflavin 3-gallate (TF2a) exhibited highest binding affinities towards RdRp, 3CLpro/Mpro and PLpro targets of SARS-CoV-2 with low docking scores of -14.92, -11.68 and -10.90 kcal/mol, respectively.	procyanidin B2	72-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	186-191
33715595-5	2021	Among the 70 tea bioactives screened, theaflavin 3,3"-di-gallate (TF3), Procyanidin B2 and Theaflavin 3-gallate (TF2a) exhibited highest binding affinities towards RdRp, 3CLpro/Mpro and PLpro targets of SARS-CoV-2 with low docking scores of -14.92, -11.68 and -10.90 kcal/mol, respectively.	Theaflavin 3-gallate	91-111	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	164-168
33715595-5	2021	Among the 70 tea bioactives screened, theaflavin 3,3"-di-gallate (TF3), Procyanidin B2 and Theaflavin 3-gallate (TF2a) exhibited highest binding affinities towards RdRp, 3CLpro/Mpro and PLpro targets of SARS-CoV-2 with low docking scores of -14.92, -11.68 and -10.90 kcal/mol, respectively.	Theaflavin 3-gallate	91-111	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	186-191
33682633-3	2021	Extensive docking and molecular dynamics study describing the binding of natural nucleotides (NTPs) and its analogues leading to significant structural variation in the RdRP has been presented here.	ntps	94-98	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	169-173
33682633-4	2021	RdRP simulations in its apo, NTP-bound, and analogue-bound form have been performed.	ntp	29-32	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	0-4
33041371-5	2021	Among them, desacetylgedunin (DCG) found in Neem seed showed the highest binding affinity towards PLpro.	desacetylgedunin	12-28	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	98-103
33686143-4	2021	While a prospective, multi-center clinical study is ongoing, two parallel in silico studies have proposed one of the two SARS-CoV-2 proteases, 3CLpro or PLpro, as potential molecular targets of famotidine activity; however, this remains to be experimentally validated.	Famotidine	194-204	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	153-158
33675510-6	2022	In this study, naphthyl derivatives inhibiting PLpro enzyme were subjected to robust molecular modelling approaches to understand different structural fingerprints important for the inhibition.	naphthyl	15-23	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	47-52
33675510-7	2022	Here, we cover two main aspects such as (a) exploration of naphthyl derivatives by classification QSAR analyses to find important fingerprints that module the SARS-CoV PLpro inhibition and (b) implications of naphthyl derivatives against SARS-CoV-2 PLpro enzyme through detailed ligand-receptor interaction analysis.	naphthyl	59-67	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	168-173
33675510-7	2022	Here, we cover two main aspects such as (a) exploration of naphthyl derivatives by classification QSAR analyses to find important fingerprints that module the SARS-CoV PLpro inhibition and (b) implications of naphthyl derivatives against SARS-CoV-2 PLpro enzyme through detailed ligand-receptor interaction analysis.	naphthyl	59-67	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	249-254
33041371-5	2021	Among them, desacetylgedunin (DCG) found in Neem seed showed the highest binding affinity towards PLpro.	dcg	30-33	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	98-103
33041371-6	2021	Furthermore, MD-simulation studies supported by standard analysis (e.g. root mean square deviation and fluctuation (RMSD, RMSF), radius of gyration, solvent accessible surface area (SASA)) showed large impact on the structure of PLpro by DCG.	dcg	238-241	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	229-234
33041371-7	2021	We believe that the significant effect of DCG on PLpro may help in therapeutic efforts against SARS-CoV-2.	dcg	42-45	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	49-54
33755983-7	2021	Furthermore, we evidenced the ability of remdesivir, tenofovir, emtricitabine, and lamivudine to be incorporated in SARS-CoV-2 RdRp in the same protein pocket where poses the corresponding natural nucleoside substrates with comparable Ki and activating similar interactions.	remdesivir	41-51	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	127-131
33755983-7	2021	Furthermore, we evidenced the ability of remdesivir, tenofovir, emtricitabine, and lamivudine to be incorporated in SARS-CoV-2 RdRp in the same protein pocket where poses the corresponding natural nucleoside substrates with comparable Ki and activating similar interactions.	Tenofovir	53-62	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	127-131
33755983-7	2021	Furthermore, we evidenced the ability of remdesivir, tenofovir, emtricitabine, and lamivudine to be incorporated in SARS-CoV-2 RdRp in the same protein pocket where poses the corresponding natural nucleoside substrates with comparable Ki and activating similar interactions.	Emtricitabine	64-77	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	127-131
33755983-7	2021	Furthermore, we evidenced the ability of remdesivir, tenofovir, emtricitabine, and lamivudine to be incorporated in SARS-CoV-2 RdRp in the same protein pocket where poses the corresponding natural nucleoside substrates with comparable Ki and activating similar interactions.	Lamivudine	83-93	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	127-131
33755983-7	2021	Furthermore, we evidenced the ability of remdesivir, tenofovir, emtricitabine, and lamivudine to be incorporated in SARS-CoV-2 RdRp in the same protein pocket where poses the corresponding natural nucleoside substrates with comparable Ki and activating similar interactions.	Nucleosides	197-207	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	127-131
32902889-5	2021	In comparison with SARS-CoV PLpro , in SARS-CoV-2, the PLpro had a conserved catalytic triad of C111, H278 and D293, with a slightly lower number of polar interface residues and of hydrogen bonds, a higher number of buried interface sizes and a lower number of residues that interact with ubiquitin and PLpro .	h278	102-106	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	55-60
33693066-7	2021	In this study, we have screened a library of compounds, containing approved RdRp inhibitor drugs that were or in use to treat other viruses (favipiravir, sofosbuvir, ribavirin, lopinavir, tenofovir, ritonavir, galidesivir and remdesivir) and their structural analogues, in order to identify potential inhibitors of SARS-CoV-2 RdRp.	favipiravir	141-152	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	76-80
33693066-7	2021	In this study, we have screened a library of compounds, containing approved RdRp inhibitor drugs that were or in use to treat other viruses (favipiravir, sofosbuvir, ribavirin, lopinavir, tenofovir, ritonavir, galidesivir and remdesivir) and their structural analogues, in order to identify potential inhibitors of SARS-CoV-2 RdRp.	Sofosbuvir	154-164	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	76-80
33693066-7	2021	In this study, we have screened a library of compounds, containing approved RdRp inhibitor drugs that were or in use to treat other viruses (favipiravir, sofosbuvir, ribavirin, lopinavir, tenofovir, ritonavir, galidesivir and remdesivir) and their structural analogues, in order to identify potential inhibitors of SARS-CoV-2 RdRp.	galidesivir	210-221	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	76-80
33693066-7	2021	In this study, we have screened a library of compounds, containing approved RdRp inhibitor drugs that were or in use to treat other viruses (favipiravir, sofosbuvir, ribavirin, lopinavir, tenofovir, ritonavir, galidesivir and remdesivir) and their structural analogues, in order to identify potential inhibitors of SARS-CoV-2 RdRp.	remdesivir	226-236	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	76-80
33531790-10	2021	The bioinformatic analysis revealed a higher binding efficiency of CPT and its derivatives, toptecan and irinotecan against Mpro and RdRp.	toptecan	92-100	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	133-137
32902889-5	2021	In comparison with SARS-CoV PLpro , in SARS-CoV-2, the PLpro had a conserved catalytic triad of C111, H278 and D293, with a slightly lower number of polar interface residues and of hydrogen bonds, a higher number of buried interface sizes and a lower number of residues that interact with ubiquitin and PLpro .	h278	102-106	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	55-60
33531790-10	2021	The bioinformatic analysis revealed a higher binding efficiency of CPT and its derivatives, toptecan and irinotecan against Mpro and RdRp.	Irinotecan	105-115	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	133-137
32902889-5	2021	In comparison with SARS-CoV PLpro , in SARS-CoV-2, the PLpro had a conserved catalytic triad of C111, H278 and D293, with a slightly lower number of polar interface residues and of hydrogen bonds, a higher number of buried interface sizes and a lower number of residues that interact with ubiquitin and PLpro .	Hydrogen	181-189	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	55-60
32902889-5	2021	In comparison with SARS-CoV PLpro , in SARS-CoV-2, the PLpro had a conserved catalytic triad of C111, H278 and D293, with a slightly lower number of polar interface residues and of hydrogen bonds, a higher number of buried interface sizes and a lower number of residues that interact with ubiquitin and PLpro .	Hydrogen	181-189	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	55-60
33034398-5	2021	Quercetin inhibits 3CLpro and PLpro with a docking binding energy corresponding to -6.25 and -4.62 kcal/mol, respectively.	Quercetin	0-9	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	30-35
33640032-2	2021	RESULTS: We herein identified two natural products, ginkgolic acid and anacardic acid, as inhibitors using a high-throughput screen targeting the SARS-CoV-2 papain-like protease (PLpro).	ginkgolic acid	52-66	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	179-184
33640032-2	2021	RESULTS: We herein identified two natural products, ginkgolic acid and anacardic acid, as inhibitors using a high-throughput screen targeting the SARS-CoV-2 papain-like protease (PLpro).	anacardic acid	71-85	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	179-184
33615998-7	2021	Some of these compounds gave better K i, binding energy and logP values when compared to standard RdRp inhibitors, such as remdesivir (REM) (K i = 15.61 muM, logP = 2.2; binding energy = -6.95), a clinically approved RdRp inhibitor and nine other RdRp inhibitors.	remdesivir	123-133	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	98-102
33421473-6	2021	In-silico screening, molecular mechanics, molecular dynamics simulation (MDS) analysis suggest ribavirin, and remdesivir have good interaction with the binding site of the RdRp protein as compared to other antiviral investigated.	Ribavirin	95-104	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	172-176
33421473-6	2021	In-silico screening, molecular mechanics, molecular dynamics simulation (MDS) analysis suggest ribavirin, and remdesivir have good interaction with the binding site of the RdRp protein as compared to other antiviral investigated.	remdesivir	110-120	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	172-176
33716752-7	2021	Tellimagrandin I, SaikosaponinB2, Hesperidin and (-)-Epigallocatechin Gallate were the most prominent ones that showed strong binding affinity toward RdRp.	tellimagrandin I	0-16	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	150-154
33716752-7	2021	Tellimagrandin I, SaikosaponinB2, Hesperidin and (-)-Epigallocatechin Gallate were the most prominent ones that showed strong binding affinity toward RdRp.	saikosaponin D	18-32	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	150-154
33716752-7	2021	Tellimagrandin I, SaikosaponinB2, Hesperidin and (-)-Epigallocatechin Gallate were the most prominent ones that showed strong binding affinity toward RdRp.	Hesperidin	34-44	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	150-154
33716752-7	2021	Tellimagrandin I, SaikosaponinB2, Hesperidin and (-)-Epigallocatechin Gallate were the most prominent ones that showed strong binding affinity toward RdRp.	epigallocatechin gallate	49-77	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	150-154
33671652-4	2021	Peptides of five to six amino acids with a basic amnio acid in the head, acidic amnio acid in the neck, hydrophobicity group in the middle, and basic amino acids in the tail showed higher binding to COVID-19 virus main protease (Mpro), while those with basic amino acids and acidic amino acids in the two sides and aromatic amino acids in the middle might have stronger interaction with COVID-19 virus RNA-dependent RNA polymerase (RdRp).	Amino Acids, Basic	144-161	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	432-436
33615998-7	2021	Some of these compounds gave better K i, binding energy and logP values when compared to standard RdRp inhibitors, such as remdesivir (REM) (K i = 15.61 muM, logP = 2.2; binding energy = -6.95), a clinically approved RdRp inhibitor and nine other RdRp inhibitors.	remdesivir	123-133	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	217-221
33615998-7	2021	Some of these compounds gave better K i, binding energy and logP values when compared to standard RdRp inhibitors, such as remdesivir (REM) (K i = 15.61 muM, logP = 2.2; binding energy = -6.95), a clinically approved RdRp inhibitor and nine other RdRp inhibitors.	remdesivir	123-133	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	217-221
33615998-7	2021	Some of these compounds gave better K i, binding energy and logP values when compared to standard RdRp inhibitors, such as remdesivir (REM) (K i = 15.61 muM, logP = 2.2; binding energy = -6.95), a clinically approved RdRp inhibitor and nine other RdRp inhibitors.	remdesivir	135-138	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	98-102
33615998-7	2021	Some of these compounds gave better K i, binding energy and logP values when compared to standard RdRp inhibitors, such as remdesivir (REM) (K i = 15.61 muM, logP = 2.2; binding energy = -6.95), a clinically approved RdRp inhibitor and nine other RdRp inhibitors.	remdesivir	135-138	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	217-221
33615998-7	2021	Some of these compounds gave better K i, binding energy and logP values when compared to standard RdRp inhibitors, such as remdesivir (REM) (K i = 15.61 muM, logP = 2.2; binding energy = -6.95), a clinically approved RdRp inhibitor and nine other RdRp inhibitors.	remdesivir	135-138	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	217-221
33615998-9	2021	Molecular dynamics simulations (MDSs) showed that the selected RdRp-IBD complexes were highly stable compared to the native RdRp and RdRp-REM complex during 100 ns time periods.	remdesivir	138-141	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	63-67
33565387-3	2021	Here, the mechanisms of the inhibition of the RNA-dependent RNA polymerase (RdRp), responsible for the replication of the virus in host cells, are examined by different ligands, such as Remdesivir (RDV), Remdesivir monophosphate (RMP), and several artificially expanded genetic information systems (AEGISs) including their different sequences by employing molecular docking, MD simulations, and MM/GBSA techniques.	remdesivir	186-196	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	76-80
33599180-7	2021	Tegobuvir (19) and compound 45 showed the best binding affinity toward RdRp and 3Clpro of SARS-CoV-2 in silico, respectively.	tegobuvir	0-9	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	71-75
33599180-8	2021	Tegobuvir -previously applied for hepatitis C virus- formed highly stable complex with uncommon binding pocket of RdRp (E total: -707.91 Kcal/mol) in silico.	tegobuvir	0-9	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	114-118
33526596-2	2021	Here we report the structure of favipiravir ribonucleoside triphosphate (favipiravir-RTP) in complex with the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) bound to a template:primer RNA duplex, determined by electron cryomicroscopy (cryoEM) to a resolution of 2.5 A.	favipiravir ribonucleoside triphosphate	32-71	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	151-155
33526596-2	2021	Here we report the structure of favipiravir ribonucleoside triphosphate (favipiravir-RTP) in complex with the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) bound to a template:primer RNA duplex, determined by electron cryomicroscopy (cryoEM) to a resolution of 2.5 A.	UNII-F0JG9C0OQD	73-88	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	151-155
33565387-3	2021	Here, the mechanisms of the inhibition of the RNA-dependent RNA polymerase (RdRp), responsible for the replication of the virus in host cells, are examined by different ligands, such as Remdesivir (RDV), Remdesivir monophosphate (RMP), and several artificially expanded genetic information systems (AEGISs) including their different sequences by employing molecular docking, MD simulations, and MM/GBSA techniques.	remdesivir	198-201	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	76-80
33565387-3	2021	Here, the mechanisms of the inhibition of the RNA-dependent RNA polymerase (RdRp), responsible for the replication of the virus in host cells, are examined by different ligands, such as Remdesivir (RDV), Remdesivir monophosphate (RMP), and several artificially expanded genetic information systems (AEGISs) including their different sequences by employing molecular docking, MD simulations, and MM/GBSA techniques.	remdesivir	204-214	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	76-80
33565387-3	2021	Here, the mechanisms of the inhibition of the RNA-dependent RNA polymerase (RdRp), responsible for the replication of the virus in host cells, are examined by different ligands, such as Remdesivir (RDV), Remdesivir monophosphate (RMP), and several artificially expanded genetic information systems (AEGISs) including their different sequences by employing molecular docking, MD simulations, and MM/GBSA techniques.	monophosphate	215-228	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	76-80
33565387-3	2021	Here, the mechanisms of the inhibition of the RNA-dependent RNA polymerase (RdRp), responsible for the replication of the virus in host cells, are examined by different ligands, such as Remdesivir (RDV), Remdesivir monophosphate (RMP), and several artificially expanded genetic information systems (AEGISs) including their different sequences by employing molecular docking, MD simulations, and MM/GBSA techniques.	rmp	230-233	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	76-80
33565387-4	2021	It is found that the binding of RDV to RdRp may block the RNA binding site.	remdesivir	32-35	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	39-43
33565387-8	2021	It is shown that dPdZ, a two-nucleotide sequence containing P and Z would bind to RdRp very strongly and may occupy the positions of two nucleotides in the RNA strand, thereby denying access of the substrate-binding site to the viral RNA.	dpdz	17-21	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	82-86
33472860-2	2021	Previously, self-GMPylation/UMPylation activities were reported for an arterivirus NiRAN-RdRp nsp and suggested to generate a transient state primed for transferring nucleoside monophosphate (NMP) to (currently unknown) viral and/or cellular biopolymers.	nucleoside monophosphate	166-190	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	89-93
33472860-2	2021	Previously, self-GMPylation/UMPylation activities were reported for an arterivirus NiRAN-RdRp nsp and suggested to generate a transient state primed for transferring nucleoside monophosphate (NMP) to (currently unknown) viral and/or cellular biopolymers.	N-methylpyrrolidone	192-195	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	89-93
33472860-3	2021	Here, we show that the coronavirus (human coronavirus [HCoV]-229E and severe acute respiratory syndrome coronavirus 2) nsp12 (NiRAN-RdRp) has Mn2+-dependent NMPylation activity that catalyzes the transfer of a single NMP to the cognate nsp9 by forming a phosphoramidate bond with the primary amine at the nsp9 N terminus (N3825) following Mpro-mediated proteolytic release of nsp9 from N-terminally flanking nsps.	Manganese(2+)	142-146	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	132-136
33472860-3	2021	Here, we show that the coronavirus (human coronavirus [HCoV]-229E and severe acute respiratory syndrome coronavirus 2) nsp12 (NiRAN-RdRp) has Mn2+-dependent NMPylation activity that catalyzes the transfer of a single NMP to the cognate nsp9 by forming a phosphoramidate bond with the primary amine at the nsp9 N terminus (N3825) following Mpro-mediated proteolytic release of nsp9 from N-terminally flanking nsps.	Manganese(2+)	142-146	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	236-240
33472860-3	2021	Here, we show that the coronavirus (human coronavirus [HCoV]-229E and severe acute respiratory syndrome coronavirus 2) nsp12 (NiRAN-RdRp) has Mn2+-dependent NMPylation activity that catalyzes the transfer of a single NMP to the cognate nsp9 by forming a phosphoramidate bond with the primary amine at the nsp9 N terminus (N3825) following Mpro-mediated proteolytic release of nsp9 from N-terminally flanking nsps.	Manganese(2+)	142-146	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	305-309
33472860-3	2021	Here, we show that the coronavirus (human coronavirus [HCoV]-229E and severe acute respiratory syndrome coronavirus 2) nsp12 (NiRAN-RdRp) has Mn2+-dependent NMPylation activity that catalyzes the transfer of a single NMP to the cognate nsp9 by forming a phosphoramidate bond with the primary amine at the nsp9 N terminus (N3825) following Mpro-mediated proteolytic release of nsp9 from N-terminally flanking nsps.	Manganese(2+)	142-146	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	305-309
33472860-3	2021	Here, we show that the coronavirus (human coronavirus [HCoV]-229E and severe acute respiratory syndrome coronavirus 2) nsp12 (NiRAN-RdRp) has Mn2+-dependent NMPylation activity that catalyzes the transfer of a single NMP to the cognate nsp9 by forming a phosphoramidate bond with the primary amine at the nsp9 N terminus (N3825) following Mpro-mediated proteolytic release of nsp9 from N-terminally flanking nsps.	phosphoramidic acid	254-269	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	132-136
33472860-3	2021	Here, we show that the coronavirus (human coronavirus [HCoV]-229E and severe acute respiratory syndrome coronavirus 2) nsp12 (NiRAN-RdRp) has Mn2+-dependent NMPylation activity that catalyzes the transfer of a single NMP to the cognate nsp9 by forming a phosphoramidate bond with the primary amine at the nsp9 N terminus (N3825) following Mpro-mediated proteolytic release of nsp9 from N-terminally flanking nsps.	phosphoramidic acid	254-269	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	236-240
33472860-3	2021	Here, we show that the coronavirus (human coronavirus [HCoV]-229E and severe acute respiratory syndrome coronavirus 2) nsp12 (NiRAN-RdRp) has Mn2+-dependent NMPylation activity that catalyzes the transfer of a single NMP to the cognate nsp9 by forming a phosphoramidate bond with the primary amine at the nsp9 N terminus (N3825) following Mpro-mediated proteolytic release of nsp9 from N-terminally flanking nsps.	phosphoramidic acid	254-269	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	305-309
33472860-3	2021	Here, we show that the coronavirus (human coronavirus [HCoV]-229E and severe acute respiratory syndrome coronavirus 2) nsp12 (NiRAN-RdRp) has Mn2+-dependent NMPylation activity that catalyzes the transfer of a single NMP to the cognate nsp9 by forming a phosphoramidate bond with the primary amine at the nsp9 N terminus (N3825) following Mpro-mediated proteolytic release of nsp9 from N-terminally flanking nsps.	phosphoramidic acid	254-269	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	305-309
33472860-3	2021	Here, we show that the coronavirus (human coronavirus [HCoV]-229E and severe acute respiratory syndrome coronavirus 2) nsp12 (NiRAN-RdRp) has Mn2+-dependent NMPylation activity that catalyzes the transfer of a single NMP to the cognate nsp9 by forming a phosphoramidate bond with the primary amine at the nsp9 N terminus (N3825) following Mpro-mediated proteolytic release of nsp9 from N-terminally flanking nsps.	Amines	292-297	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	132-136
33472860-3	2021	Here, we show that the coronavirus (human coronavirus [HCoV]-229E and severe acute respiratory syndrome coronavirus 2) nsp12 (NiRAN-RdRp) has Mn2+-dependent NMPylation activity that catalyzes the transfer of a single NMP to the cognate nsp9 by forming a phosphoramidate bond with the primary amine at the nsp9 N terminus (N3825) following Mpro-mediated proteolytic release of nsp9 from N-terminally flanking nsps.	Amines	292-297	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	236-240
33472860-3	2021	Here, we show that the coronavirus (human coronavirus [HCoV]-229E and severe acute respiratory syndrome coronavirus 2) nsp12 (NiRAN-RdRp) has Mn2+-dependent NMPylation activity that catalyzes the transfer of a single NMP to the cognate nsp9 by forming a phosphoramidate bond with the primary amine at the nsp9 N terminus (N3825) following Mpro-mediated proteolytic release of nsp9 from N-terminally flanking nsps.	Amines	292-297	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	305-309
33472860-3	2021	Here, we show that the coronavirus (human coronavirus [HCoV]-229E and severe acute respiratory syndrome coronavirus 2) nsp12 (NiRAN-RdRp) has Mn2+-dependent NMPylation activity that catalyzes the transfer of a single NMP to the cognate nsp9 by forming a phosphoramidate bond with the primary amine at the nsp9 N terminus (N3825) following Mpro-mediated proteolytic release of nsp9 from N-terminally flanking nsps.	Amines	292-297	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	305-309
33472860-5	2021	Mutational studies using recombinant coronavirus nsp9 and nsp12 proteins and genetically engineered HCoV-229E mutants identified residues essential for NiRAN-mediated nsp9 NMPylation and virus replication in cell culture.	Parathion	152-157	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	49-53
33472860-5	2021	Mutational studies using recombinant coronavirus nsp9 and nsp12 proteins and genetically engineered HCoV-229E mutants identified residues essential for NiRAN-mediated nsp9 NMPylation and virus replication in cell culture.	Parathion	152-157	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	167-171
33472860-6	2021	The data corroborate predictions on NiRAN active-site residues and establish an essential role for the nsp9 N3826 residue in both nsp9 NMPylation in vitro and virus replication.	n3826	108-113	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	103-107
33472860-6	2021	The data corroborate predictions on NiRAN active-site residues and establish an essential role for the nsp9 N3826 residue in both nsp9 NMPylation in vitro and virus replication.	n3826	108-113	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	130-134
33309661-5	2021	A model of the SARS-CoV-2-nsp10-nsp14 complex bound to substrate RNA showed that the ritonavir binding site overlaps with that of the 3" nucleotide of substrate RNA.	Ritonavir	85-94	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	26-31
33260103-0	2021	Mechanistic insight on the remdesivir binding to RNA-Dependent RNA polymerase (RdRp) of SARS-cov-2.	remdesivir	27-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	79-83
33260103-2	2021	Remdesivir (RDV) is clinically used drug which targets RdRp, however its mechanism of action remains elusive.	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	55-59
33260103-2	2021	Remdesivir (RDV) is clinically used drug which targets RdRp, however its mechanism of action remains elusive.	remdesivir	12-15	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	55-59
33260103-3	2021	This study aims to find out the binding dynamics of active Remdesivir-triphosphate (RDV-TP) to RdRp by means of molecular dynamics (MD) simulation.	remdesivir	59-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	95-99
33260103-3	2021	This study aims to find out the binding dynamics of active Remdesivir-triphosphate (RDV-TP) to RdRp by means of molecular dynamics (MD) simulation.	remdesivir	84-87	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	95-99
33260103-4	2021	We built a homology model of RdRp along with RNA and manganese ion using RdRp hepatitis C virus and recent SARS-CoV-2 structures.	Manganese	53-62	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	73-77
33260103-6	2021	We then employed the model to study the binding of RDV-TP to RdRp during three independent 500 ns MD simulations.	remdesivir	51-54	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	61-65
33281478-2	2021	The recent elucidation of the experimental structure of SARS-CoV-2 RdRp enzyme complexed with triphosphate form of Remdesivir (RTP) has opened an avenue for structure-based identification of potent inhibitors.	remdesivir	115-125	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	67-71
33412235-7	2021	On comparison with the known SARS-CoV-2 protease inhibitor -lopinavir and RdRp inhibitor -remdesivir, apigenin-o-7-glucuronide was found to be a phenomenal inhibitor of both protease and polymerase, as it strongly interacts with their active sites and exhibited remarkably high binding affinity.	apigenin-o-7-glucuronide	102-126	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	74-78
33281478-0	2021	The potential of Paritaprevir and Emetine as inhibitors of SARS-CoV-2 RdRp.	paritaprevir	17-29	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	70-74
33281478-0	2021	The potential of Paritaprevir and Emetine as inhibitors of SARS-CoV-2 RdRp.	Emetine	34-41	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	70-74
33281478-2	2021	The recent elucidation of the experimental structure of SARS-CoV-2 RdRp enzyme complexed with triphosphate form of Remdesivir (RTP) has opened an avenue for structure-based identification of potent inhibitors.	triphosphoric acid	94-106	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	67-71
33387885-7	2021	The formation of two strong hydrogen bonds between N-(4[(2E)-3-(phenyl)-1-(phenyl)-prop-2-en-1-one]) acetamide (PAAB) and the NSP16-NSP10 heterodimer methyltransferase was also noted.	n-(4[(2e)-3-(phenyl)-1-(phenyl)-prop-2-en-1-one]) acetamide	51-110	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	132-137
32943188-3	2021	Remdesivir targets the RNA-dependent RNA polymerase (RdRp), an essential enzyme for viral RNA replication and a promising drug target for COVID-19.	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	53-57
32943188-4	2021	Recently, several structures of RdRp in complex with substrate RNA and remdesivir were reported, providing insights into the mechanisms of RNA recognition by RdRp.	remdesivir	71-81	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	32-36
32943188-4	2021	Recently, several structures of RdRp in complex with substrate RNA and remdesivir were reported, providing insights into the mechanisms of RNA recognition by RdRp.	remdesivir	71-81	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	158-162
33492492-5	2021	In this current study, 16 derivatives of gallic acid were docked against five selected non-structural proteins of SARS-COV-2 known to be a good target for finding small molecule inhibitors against the virus, namely, nsp3, nsp5, nsp12, nsp13, and nsp14.	Gallic Acid	41-52	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	216-220
33492492-8	2021	RESULTS: 4-O-(6-galloylglucoside) gave binding energy values of - 8.4, - 6.8, - 8.9, - 9.1, and - 7.5 kcal/mol against Mpro, nsp3, nsp12, nsp13, and nsp15 respectively.	4-o-(6-galloylglucoside	9-32	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	125-129
33387885-7	2021	The formation of two strong hydrogen bonds between N-(4[(2E)-3-(phenyl)-1-(phenyl)-prop-2-en-1-one]) acetamide (PAAB) and the NSP16-NSP10 heterodimer methyltransferase was also noted.	Hydrogen	28-36	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	132-137
33491569-2	2021	In this report, a computational study is performed to offer insights on the binding of Remdesivir and Galidesivir with SARS-CoV2 RdRp with natural substrate, ATP, as the control.	remdesivir	87-97	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	129-133
33491569-2	2021	In this report, a computational study is performed to offer insights on the binding of Remdesivir and Galidesivir with SARS-CoV2 RdRp with natural substrate, ATP, as the control.	Adenosine Triphosphate	158-161	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	129-133
33491569-4	2021	ATP also displayed comparative and strong binding free energy of -6.3 kcal/mole in the catalytic site of RdRp.	Adenosine Triphosphate	0-3	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	105-109
33491569-9	2021	Remdesivir also binds at the catalytic site and showed high potency to inhibit the function of RdRp.	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	95-99
33491569-10	2021	Binding of co-factor units nsp7 and nsp8 with RdRp (nsp12) complexed with Remdesivir and Galidesivir was also examined.	remdesivir	74-84	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	27-31
33491569-10	2021	Binding of co-factor units nsp7 and nsp8 with RdRp (nsp12) complexed with Remdesivir and Galidesivir was also examined.	remdesivir	74-84	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	36-40
33491569-10	2021	Binding of co-factor units nsp7 and nsp8 with RdRp (nsp12) complexed with Remdesivir and Galidesivir was also examined.	remdesivir	74-84	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	46-50
33491569-10	2021	Binding of co-factor units nsp7 and nsp8 with RdRp (nsp12) complexed with Remdesivir and Galidesivir was also examined.	galidesivir	89-100	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	27-31
33491569-10	2021	Binding of co-factor units nsp7 and nsp8 with RdRp (nsp12) complexed with Remdesivir and Galidesivir was also examined.	galidesivir	89-100	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	36-40
33491569-10	2021	Binding of co-factor units nsp7 and nsp8 with RdRp (nsp12) complexed with Remdesivir and Galidesivir was also examined.	galidesivir	89-100	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	46-50
33491569-12	2021	Overall, this study suggests, Remdesivir has anti-RdRp activity via binding at a catalytic site.	remdesivir	30-40	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	50-54
33387885-7	2021	The formation of two strong hydrogen bonds between N-(4[(2E)-3-(phenyl)-1-(phenyl)-prop-2-en-1-one]) acetamide (PAAB) and the NSP16-NSP10 heterodimer methyltransferase was also noted.	Acedoben	112-116	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	132-137
33475021-5	2021	In our study, the antimalarial compounds have been screened and docked against SARS-CoV-2-RdRp (PDB ID: 7BTF), and it was observed that the antimalarials chloroquine, hydroxychloroquine, and amodiaquine exhibit good affinity.	Hydroxychloroquine	167-185	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-94
33478342-0	2021	In silico evaluation of lapachol derivatives binding to the Nsp9 of SARS-CoV-2.	lapachol	24-32	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	60-64
33478342-7	2021	Virtual screening by docking and molecular dynamics suggests that lapachol derivatives can interact with Nsp9 from SARS-CoV-2.	lapachol	66-74	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	105-109
33478342-8	2021	Complexes of lapachol derivatives V, VI, VIII, IX, and XI with the Nsp9 RNA binding site were subjected to molecular dynamics assays, to assess the stability of the complexes via RMSD.	lapachol	13-21	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	67-71
33478342-12	2021	In addition, we showed that lapachol derivatives are potential ligands for SARS-CoV-2 Nsp9.	lapachol	28-36	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	86-90
33475021-8	2021	The amino acid residues involved in the binding of ATP in the case of poliovirus-RdRp and residues involved in binding with the antimalarial compounds with SARS-CoV-2-RdRp were compared.	Adenosine Triphosphate	51-54	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	81-85
33475021-5	2021	In our study, the antimalarial compounds have been screened and docked against SARS-CoV-2-RdRp (PDB ID: 7BTF), and it was observed that the antimalarials chloroquine, hydroxychloroquine, and amodiaquine exhibit good affinity.	Amodiaquine	191-202	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-94
33475021-11	2021	Further residues involved in binding of antimalarials with SARS-CoV-2-RdRp were compared with the residues involved in the SARS-CoV-2-RdRp complexed with remdesivir [PDB ID: 7BV2].	remdesivir	154-164	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	134-138
33475021-12	2021	It was observed that co-crystallized remdesivir and docked antimalarials bind in the same pocket of SARS-CoV-2 -RdRp.	remdesivir	37-47	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	112-116
33842834-8	2021	The results of our analysis with some other suggested drugs indicated that chloroquine and hydroxychloroquine had high binding energy (low inhibitory effect) with all three proteins-Mpro, PLpro, and RdRp.	Chloroquine	75-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	188-193
33459176-9	2021	oleanolic acid, ursolic acid, 3beta-acetoxyolean-12-en-27-oic acid and isovitexin followed by the binding free energy calculations using MM-GBSA and these molecules have stable interactions with PLpro protein binding site.	Oleanolic Acid	0-14	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	195-200
33459176-9	2021	oleanolic acid, ursolic acid, 3beta-acetoxyolean-12-en-27-oic acid and isovitexin followed by the binding free energy calculations using MM-GBSA and these molecules have stable interactions with PLpro protein binding site.	ursolic acid	16-28	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	195-200
33459176-9	2021	oleanolic acid, ursolic acid, 3beta-acetoxyolean-12-en-27-oic acid and isovitexin followed by the binding free energy calculations using MM-GBSA and these molecules have stable interactions with PLpro protein binding site.	CHEMBL208639	30-66	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	195-200
33223560-4	2021	Lurasidone and its derivatives displayed substantial binding affinity against five proteins (Mpro, PLpro, Spro, helicase and RdRp).	Lurasidone Hydrochloride	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-104
33223560-4	2021	Lurasidone and its derivatives displayed substantial binding affinity against five proteins (Mpro, PLpro, Spro, helicase and RdRp).	Lurasidone Hydrochloride	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	125-129
33842834-8	2021	The results of our analysis with some other suggested drugs indicated that chloroquine and hydroxychloroquine had high binding energy (low inhibitory effect) with all three proteins-Mpro, PLpro, and RdRp.	Chloroquine	75-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	199-203
33842834-8	2021	The results of our analysis with some other suggested drugs indicated that chloroquine and hydroxychloroquine had high binding energy (low inhibitory effect) with all three proteins-Mpro, PLpro, and RdRp.	Hydroxychloroquine	91-109	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	188-193
33842834-8	2021	The results of our analysis with some other suggested drugs indicated that chloroquine and hydroxychloroquine had high binding energy (low inhibitory effect) with all three proteins-Mpro, PLpro, and RdRp.	Hydroxychloroquine	91-109	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	199-203
33427588-3	2021	In this present study, we have predicted the reported bioactive flavonoids and triterpenoids of the plant against the SARS-CoV-2 main protease, RNA-dependent RNA polymerase (RdRp), spike protein, angiotensin converting enzyme (ACE-2) receptor and dipeptidyl peptidase (DPP4) receptor through molecular docking and in silico ADME predictions methods.	Flavonoids	64-74	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-178
33249077-0	2021	Flavonols as potential antiviral drugs targeting SARS-CoV-2 proteases (3CLpro and PLpro), spike protein, RNA-dependent RNA polymerase (RdRp) and angiotensin-converting enzyme II receptor (ACE2).	Flavonols	0-9	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	82-87
33249077-0	2021	Flavonols as potential antiviral drugs targeting SARS-CoV-2 proteases (3CLpro and PLpro), spike protein, RNA-dependent RNA polymerase (RdRp) and angiotensin-converting enzyme II receptor (ACE2).	Flavonols	0-9	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	135-139
33249077-5	2021	In this context, the present study reviews the efficacy of many dietary flavonols as potential antiviral drugs targeting the SARS-CoV-2 enzymes and proteins including Chymotrypsin-Like Protease (3CLpro), Papain Like protease (PLpro), Spike protein (S protein) and RNA-dependent RNA polymerase (RdRp), and also their ability to interact with the angiotensin-converting enzyme II (ACE2) receptor.	Flavonols	72-81	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	226-231
33249077-5	2021	In this context, the present study reviews the efficacy of many dietary flavonols as potential antiviral drugs targeting the SARS-CoV-2 enzymes and proteins including Chymotrypsin-Like Protease (3CLpro), Papain Like protease (PLpro), Spike protein (S protein) and RNA-dependent RNA polymerase (RdRp), and also their ability to interact with the angiotensin-converting enzyme II (ACE2) receptor.	Flavonols	72-81	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	294-298
33436624-2	2021	The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2.	remdesivir	19-29	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	105-109
33436624-3	2021	Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls.	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	34-38
33436624-4	2021	Here we use synthetic RNA chemistry, biochemistry and cryo-electron microscopy to establish the molecular mechanism of remdesivir-induced RdRp stalling.	remdesivir	119-129	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	138-142
33436624-6	2021	This translocation barrier causes retention of the RNA 3"-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RdRp.	3"-nucleotide	55-68	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	106-110
33436624-6	2021	This translocation barrier causes retention of the RNA 3"-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RdRp.	3"-nucleotide	55-68	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	191-195
33436624-6	2021	This translocation barrier causes retention of the RNA 3"-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RdRp.	[[(2R,3S,4R,5S)-3,4-dihydroxy-5-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	149-172	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	106-110
33436624-6	2021	This translocation barrier causes retention of the RNA 3"-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RdRp.	[[(2R,3S,4R,5S)-3,4-dihydroxy-5-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	149-172	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	191-195
33427588-3	2021	In this present study, we have predicted the reported bioactive flavonoids and triterpenoids of the plant against the SARS-CoV-2 main protease, RNA-dependent RNA polymerase (RdRp), spike protein, angiotensin converting enzyme (ACE-2) receptor and dipeptidyl peptidase (DPP4) receptor through molecular docking and in silico ADME predictions methods.	Triterpenes	79-92	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-178
33649734-6	2021	This study selected these drugs for MD simulation investigation whose results demonstrated that ledipasvir with ACE2, estradiol benzoate with CD147, and vancomycin with RDRP represented the most favorable DeltaG.	ledipasvir	96-106	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	169-173
33389560-11	2021	CoViTris2020 strongly inhibits coronaviral-2 RdRp with exceptionally lower inhibitory binding energy of - 12.00 kcal/mol.	covitris2020	0-12	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	45-49
33389441-3	2022	In this study, detailed molecular docking and dynamics simulations are used to evaluate the binding affinity of a clinically approved drug, sofosbuvir, with the solved structure of the viral protein RNA-dependent RNA polymerase (RdRp) and compare it to the clinically approved drug, Remdesivir.	Sofosbuvir	140-150	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	229-233
33389441-3	2022	In this study, detailed molecular docking and dynamics simulations are used to evaluate the binding affinity of a clinically approved drug, sofosbuvir, with the solved structure of the viral protein RNA-dependent RNA polymerase (RdRp) and compare it to the clinically approved drug, Remdesivir.	remdesivir	283-293	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	229-233
33389441-9	2022	The interaction of SARS-CoV-2 RdRp as a target with the active form of sofosbuvir as a ligand demonstrates binding effectiveness.	Sofosbuvir	71-81	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	30-34
33389441-11	2022	Sofosbuvir was found to bind nsp12 with comparable binding energies to that of Remdesivir, which has been reported for its potential against COVID-19 RdRp and is currently approved by the FDA.	Sofosbuvir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	150-154
33389441-11	2022	Sofosbuvir was found to bind nsp12 with comparable binding energies to that of Remdesivir, which has been reported for its potential against COVID-19 RdRp and is currently approved by the FDA.	remdesivir	79-89	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	150-154
32895623-9	2021	We demonstrate that a potent SARS-CoV PLpro inhibitor GRL0617 is highly effective in inhibiting protease activity of SARS-CoV-2 with the IC50 of 2.2+-0.3 mumol/L.	GRL0617	54-61	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	38-43
33727782-5	2021	Results: The binding affinity of caryophyllene oxide was the highest on 3CLpro (- 6.0 kcal/mol), NSP3 (- 6.3 kcal/mol), NSP9 (- 6.3 kcal/mol), and RDRP (- 6.9 kcal/mol) targets, while alpha-bergamotene gave the best binding affinity on RPIA (5.7 kcal/mol) target.	caryophyllene oxide	33-52	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	97-101
33727782-5	2021	Results: The binding affinity of caryophyllene oxide was the highest on 3CLpro (- 6.0 kcal/mol), NSP3 (- 6.3 kcal/mol), NSP9 (- 6.3 kcal/mol), and RDRP (- 6.9 kcal/mol) targets, while alpha-bergamotene gave the best binding affinity on RPIA (5.7 kcal/mol) target.	caryophyllene oxide	33-52	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	120-124
33727782-5	2021	Results: The binding affinity of caryophyllene oxide was the highest on 3CLpro (- 6.0 kcal/mol), NSP3 (- 6.3 kcal/mol), NSP9 (- 6.3 kcal/mol), and RDRP (- 6.9 kcal/mol) targets, while alpha-bergamotene gave the best binding affinity on RPIA (5.7 kcal/mol) target.	caryophyllene oxide	33-52	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	147-151
33649734-6	2021	This study selected these drugs for MD simulation investigation whose results demonstrated that ledipasvir with ACE2, estradiol benzoate with CD147, and vancomycin with RDRP represented the most favorable DeltaG.	Vancomycin	153-163	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	169-173
33649734-7	2021	Also, paritaprevir and vancomycin have good binding energy with both targets (ACE2 and RdRp).	paritaprevir	6-18	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	87-91
33649734-7	2021	Also, paritaprevir and vancomycin have good binding energy with both targets (ACE2 and RdRp).	Vancomycin	23-33	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	87-91
33347311-5	2021	The inhibitors of the virus entry to cells and RdRp, such as Arbidol, remdesivir, favipiravir, EIDD-2081, and ribavirin, are in clinical trials, while most of the protease inhibitors are mainly calculated by molecular docking technology, which needs in vivo and in vitro experiments to prove the effect for SARS-CoV-2.	umifenovir	61-68	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	47-51
33236142-4	2021	Thus, the present study models potential Zn binding to RdRp and the 3CLpro.	Zinc	41-43	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	55-59
32633831-5	2021	In this review, we discuss the antiviral potential of RdRp inhibitors (mainly nucleoside analogs) with an aim to provide a comprehensive account of drug discovery on SARS-CoV-2.	Nucleosides	78-88	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	54-58
33347311-5	2021	The inhibitors of the virus entry to cells and RdRp, such as Arbidol, remdesivir, favipiravir, EIDD-2081, and ribavirin, are in clinical trials, while most of the protease inhibitors are mainly calculated by molecular docking technology, which needs in vivo and in vitro experiments to prove the effect for SARS-CoV-2.	remdesivir	70-80	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	47-51
33347311-5	2021	The inhibitors of the virus entry to cells and RdRp, such as Arbidol, remdesivir, favipiravir, EIDD-2081, and ribavirin, are in clinical trials, while most of the protease inhibitors are mainly calculated by molecular docking technology, which needs in vivo and in vitro experiments to prove the effect for SARS-CoV-2.	favipiravir	82-93	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	47-51
33347311-5	2021	The inhibitors of the virus entry to cells and RdRp, such as Arbidol, remdesivir, favipiravir, EIDD-2081, and ribavirin, are in clinical trials, while most of the protease inhibitors are mainly calculated by molecular docking technology, which needs in vivo and in vitro experiments to prove the effect for SARS-CoV-2.	eidd-2081	95-104	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	47-51
33347311-5	2021	The inhibitors of the virus entry to cells and RdRp, such as Arbidol, remdesivir, favipiravir, EIDD-2081, and ribavirin, are in clinical trials, while most of the protease inhibitors are mainly calculated by molecular docking technology, which needs in vivo and in vitro experiments to prove the effect for SARS-CoV-2.	Ribavirin	110-119	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	47-51
33110386-9	2021	Among the lead compounds, agathisflavone showed highest binding energy value of -8.4 kcal/mol against main protease, Albireodelphin showed highest dock score of -9.8 kcal/mol and -11.2 kcal/mol against RdRp, and spike proteins, respectively.	agathisflavone	26-40	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	202-206
33287144-1	2020	The RNA-dependent RNA polymerase (RdRp) is an essential enzyme for the viral replication process, catalyzing the viral RNA synthesis using a metal ion-dependent mechanism.	Metals	141-146	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	34-38
33382685-0	2020	A novel virtual screening procedure identifies Pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro.	10-propargyl-10-deazaaminopterin	47-59	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	87-91
33490902-0	2021	High-throughput rational design of the remdesivir binding site in the RdRp of SARS-CoV-2: implications for potential resistance.	remdesivir	39-49	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	70-74
33490902-3	2021	Using a rational ligand-based interface design complemented with mutational mapping, we generated a total of 100,000 mutations and provided insight into the functional outcomes of mutations in the remdesivir-binding site in nsp12 subunit of RdRp.	remdesivir	197-207	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	241-245
33283177-1	2020	COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently being treated using Remdesivir, a nucleoside analog that inhibits the RNA-dependent-RNA polymerase (RdRp).	remdesivir	124-134	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	204-208
33317409-7	2022	Docking results indicated that the nsp16/nsp10 complex has the best binding affinities where the strongest binding was detected with apigenin-7-O-rutinoside, prunin and acaciin with -9.4, -9.3 and -9.3 kcal/mol binding energy, respectively, compared to the control (SAM) with -8.2 kcal/mol.	apigenin-7-O-rutinoside	133-156	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	41-46
33317409-7	2022	Docking results indicated that the nsp16/nsp10 complex has the best binding affinities where the strongest binding was detected with apigenin-7-O-rutinoside, prunin and acaciin with -9.4, -9.3 and -9.3 kcal/mol binding energy, respectively, compared to the control (SAM) with -8.2 kcal/mol.	prunin	158-164	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	41-46
33317409-7	2022	Docking results indicated that the nsp16/nsp10 complex has the best binding affinities where the strongest binding was detected with apigenin-7-O-rutinoside, prunin and acaciin with -9.4, -9.3 and -9.3 kcal/mol binding energy, respectively, compared to the control (SAM) with -8.2 kcal/mol.	linarin	169-176	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	41-46
33305304-6	2020	A binding model is used to confirm the interactions between lisinopril and ACE on the surface of cells, as well as remdesivir and its intracellular targeting protein (RNA-dependent RNA polymerase (RdRp)).	remdesivir	115-125	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	197-201
33264025-3	2020	Among them, remdesivir, which can block the activity of RNA-dependent RNA polymerase (RdRp) in old SARS-CoV and MERS-CoV viruses, has been prescribed to COVID-19 patients in many countries.	remdesivir	12-22	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	86-90
33264025-7	2020	The binding mechanisms of remdesivir to two targets differ in that the electrostatic interaction is the main force in stabilizing the RdRp-remdesivir complex, while the van der Waals interaction dominates in the Mpro-remdesivir case.	remdesivir	26-36	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	134-138
33264025-7	2020	The binding mechanisms of remdesivir to two targets differ in that the electrostatic interaction is the main force in stabilizing the RdRp-remdesivir complex, while the van der Waals interaction dominates in the Mpro-remdesivir case.	remdesivir	139-149	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	134-138
33264025-7	2020	The binding mechanisms of remdesivir to two targets differ in that the electrostatic interaction is the main force in stabilizing the RdRp-remdesivir complex, while the van der Waals interaction dominates in the Mpro-remdesivir case.	remdesivir	139-149	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	134-138
33264025-8	2020	Our result indicates that remdesivir can target not only RdRp but also Mpro, which can be invoked to explain why this drug is effective in treating COVID-19.	remdesivir	26-36	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	57-61
33263384-9	2020	Common nsp4 interactors include N-linked glycosylation machinery, unfolded protein response associated proteins, and antiviral innate immune signaling factors.	Nitrogen	32-33	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	7-11
33263384-10	2020	Both nsp2 and nsp4 interactors are strongly enriched in proteins localized at mitochondria-associated ER membranes suggesting a new functional role for modulating host processes, such as calcium homeostasis, at these organelle contact sites.	Calcium	187-194	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	5-9
33263384-10	2020	Both nsp2 and nsp4 interactors are strongly enriched in proteins localized at mitochondria-associated ER membranes suggesting a new functional role for modulating host processes, such as calcium homeostasis, at these organelle contact sites.	Calcium	187-194	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	14-18
33055254-6	2020	Under the microscope, the viral RNA replication-transcription complex in cells, which is thought to be detectable using antibodies specific for nsp3 and double stranded RNA, was observed to fall in the presence of ciclesonide in a concentration-dependent manner.	ciclesonide	214-225	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	144-148
33364229-4	2020	Naphthalene-based inhibitors, such as the well-investigated GRL-0617 compound, have been shown to possess dual effects, inhibiting both protease and deubiquitinating activity of the PLpro.	naphthalene	0-11	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	182-187
33364229-14	2020	Further, our findings indicate that in particular hypericin, rutin, and cyanidin-3-O-glucoside, represent suitable candidates for subsequent evaluation as PLpro inhibitors.	hypericin	50-59	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	155-160
33364229-14	2020	Further, our findings indicate that in particular hypericin, rutin, and cyanidin-3-O-glucoside, represent suitable candidates for subsequent evaluation as PLpro inhibitors.	Rutin	61-66	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	155-160
33364229-14	2020	Further, our findings indicate that in particular hypericin, rutin, and cyanidin-3-O-glucoside, represent suitable candidates for subsequent evaluation as PLpro inhibitors.	cyanidin-3-o-glucoside	72-94	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	155-160
33287144-2	2020	In recent years, RdRp has emerged as an optimal target for the development of antiviral drugs, as demonstrated by recent approvals of sofosbuvir and remdesivir against Hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively.	Sofosbuvir	134-144	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	17-21
33287144-2	2020	In recent years, RdRp has emerged as an optimal target for the development of antiviral drugs, as demonstrated by recent approvals of sofosbuvir and remdesivir against Hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively.	remdesivir	149-159	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	17-21
33058837-6	2020	SPT oligonucleotides contain probe binding and virus-irrelevant regions as templates for detecting SARS-CoV-2 genes (RdRP, E, and N SARS-CoV-2) by real-time RT-PCR was performed in a concentration-dependent manner.	Oligonucleotides	4-20	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	117-121
33168456-9	2020	Similarly Indinavir showed the highest binding energy of -11.5 kcal/mol against the target protein RdRp and Dolutegravir, Elbasvir, Tipranavir, Taltegravir, Grazoprevir, Daclatasvir, Glecaprevir, Ledipasvir, Pibrentasvir and Velpatasvir showed a binding energy value in range from -8 to -11.2 kcal/mol.	Indinavir	10-19	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-103
32979815-1	2020	Human ubiquitin carboxyl-terminal hydrolase-2 (USP2) inhibitors, such as thiopurine analogs, have been reported to inhibit SARS-CoV papain-like proteases (PLpro).	2-mercaptopyrazine	73-83	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	155-160
33168456-9	2020	Similarly Indinavir showed the highest binding energy of -11.5 kcal/mol against the target protein RdRp and Dolutegravir, Elbasvir, Tipranavir, Taltegravir, Grazoprevir, Daclatasvir, Glecaprevir, Ledipasvir, Pibrentasvir and Velpatasvir showed a binding energy value in range from -8 to -11.2 kcal/mol.	glecaprevir	183-194	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-103
33168456-9	2020	Similarly Indinavir showed the highest binding energy of -11.5 kcal/mol against the target protein RdRp and Dolutegravir, Elbasvir, Tipranavir, Taltegravir, Grazoprevir, Daclatasvir, Glecaprevir, Ledipasvir, Pibrentasvir and Velpatasvir showed a binding energy value in range from -8 to -11.2 kcal/mol.	ledipasvir	196-206	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-103
33168456-9	2020	Similarly Indinavir showed the highest binding energy of -11.5 kcal/mol against the target protein RdRp and Dolutegravir, Elbasvir, Tipranavir, Taltegravir, Grazoprevir, Daclatasvir, Glecaprevir, Ledipasvir, Pibrentasvir and Velpatasvir showed a binding energy value in range from -8 to -11.2 kcal/mol.	pibrentasvir	208-220	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-103
33168456-9	2020	Similarly Indinavir showed the highest binding energy of -11.5 kcal/mol against the target protein RdRp and Dolutegravir, Elbasvir, Tipranavir, Taltegravir, Grazoprevir, Daclatasvir, Glecaprevir, Ledipasvir, Pibrentasvir and Velpatasvir showed a binding energy value in range from -8 to -11.2 kcal/mol.	velpatasvir	225-236	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-103
32476594-8	2020	Further, NSP10/NSP16 methyltransferase complexed with Telbivudine, Oxytetracycline dihydrate (anti-viral), Methylgallate (anti-malarial), 2-deoxyglucose and Daphnetin (anti-cancer) from the docking score of -7.0 to -5.7 (Kcal/mol).	Telbivudine	54-65	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	9-14
32965508-0	2020	Insights into the biased activity of dextromethorphan and haloperidol towards SARS-CoV-2 NSP6: in silico binding mechanistic analysis.	Dextromethorphan	37-53	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	89-93
32965508-0	2020	Insights into the biased activity of dextromethorphan and haloperidol towards SARS-CoV-2 NSP6: in silico binding mechanistic analysis.	Haloperidol	58-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	89-93
32965508-5	2020	To explore the potential mechanisms of biased binding and activity of the two drugs, haloperidol and dextromethorphan towards NSP6, we herein utilized molecular docking-based molecular dynamics simulation studies.	Haloperidol	85-96	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-130
32965508-5	2020	To explore the potential mechanisms of biased binding and activity of the two drugs, haloperidol and dextromethorphan towards NSP6, we herein utilized molecular docking-based molecular dynamics simulation studies.	Dextromethorphan	101-117	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-130
32965508-6	2020	Our extensive analysis of the protein-drug interactions, structural and conformational dynamics, residual frustrations, and molecular switches of NSP6-drug complexes indicates that dextromethorphan binding leads to structural destabilization and increase in conformational dynamics and energetic frustrations.	Dextromethorphan	181-197	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	146-150
32965508-7	2020	On the other hand, the strong binding of haloperidol leads to minimal structural and dynamical perturbations to NSP6.	Haloperidol	41-52	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	112-116
32965508-8	2020	Thus, the structural insights of stronger binding affinity and favorable molecular interactions of haloperidol towards viral NSP6 suggests that haloperidol can be potentially explored as a candidate drug against COVID-19.	Haloperidol	99-110	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	125-129
32965508-8	2020	Thus, the structural insights of stronger binding affinity and favorable molecular interactions of haloperidol towards viral NSP6 suggests that haloperidol can be potentially explored as a candidate drug against COVID-19.	Haloperidol	144-155	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	125-129
32965508-10	2020	Antipsychotic drug, haloperidol, binds strongly to NSP6 and induces the minimal changes in structure and dynamics of NSP6.	Haloperidol	20-31	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	51-55
32965508-10	2020	Antipsychotic drug, haloperidol, binds strongly to NSP6 and induces the minimal changes in structure and dynamics of NSP6.	Haloperidol	20-31	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	117-121
32965508-11	2020	Dextromethorphan, agonist of sigma receptors, binding leads to overall destabilization of NSP6.	Dextromethorphan	0-16	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-94
33185784-0	2020	Comparison of Binding Site of Remdesivir and Its Metabolites with NSP12-NSP7-NSP8, and NSP3 of SARS CoV-2 Virus and Alternative Potential Drugs for COVID-19 Treatment.	remdesivir	30-40	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	72-76
33185784-0	2020	Comparison of Binding Site of Remdesivir and Its Metabolites with NSP12-NSP7-NSP8, and NSP3 of SARS CoV-2 Virus and Alternative Potential Drugs for COVID-19 Treatment.	remdesivir	30-40	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	77-81
33185784-4	2020	This study compared their binding sites and suggests the crystal structure of NSP3 of SARS CoV-2 virus as an alternative binding site of AMP or ADP-ribose to treat COVID-19.	Adenosine Monophosphate	137-140	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	78-82
33185784-4	2020	This study compared their binding sites and suggests the crystal structure of NSP3 of SARS CoV-2 virus as an alternative binding site of AMP or ADP-ribose to treat COVID-19.	Adenosine Diphosphate Ribose	144-154	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	78-82
32476594-8	2020	Further, NSP10/NSP16 methyltransferase complexed with Telbivudine, Oxytetracycline dihydrate (anti-viral), Methylgallate (anti-malarial), 2-deoxyglucose and Daphnetin (anti-cancer) from the docking score of -7.0 to -5.7 (Kcal/mol).	Oxytetracycline	67-92	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	9-14
32476594-8	2020	Further, NSP10/NSP16 methyltransferase complexed with Telbivudine, Oxytetracycline dihydrate (anti-viral), Methylgallate (anti-malarial), 2-deoxyglucose and Daphnetin (anti-cancer) from the docking score of -7.0 to -5.7 (Kcal/mol).	methyl gallate	107-120	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	9-14
32476594-8	2020	Further, NSP10/NSP16 methyltransferase complexed with Telbivudine, Oxytetracycline dihydrate (anti-viral), Methylgallate (anti-malarial), 2-deoxyglucose and Daphnetin (anti-cancer) from the docking score of -7.0 to -5.7 (Kcal/mol).	Deoxyglucose	138-152	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	9-14
32476594-8	2020	Further, NSP10/NSP16 methyltransferase complexed with Telbivudine, Oxytetracycline dihydrate (anti-viral), Methylgallate (anti-malarial), 2-deoxyglucose and Daphnetin (anti-cancer) from the docking score of -7.0 to -5.7 (Kcal/mol).	daphnetin	157-166	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	9-14
33335812-8	2020	The results reveal that two drugs, docetaxel and neohesperidin, showed strong binding profiles with SARS CoV-2 RdRP.	Docetaxel	35-44	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
33251975-4	2022	Small molecules such as lopinavir and favipiravir significantly inhibit the activity of Mpro and RdRp in vitro.	Lopinavir	24-33	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	97-101
33251975-4	2022	Small molecules such as lopinavir and favipiravir significantly inhibit the activity of Mpro and RdRp in vitro.	favipiravir	38-49	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	97-101
33251975-5	2022	Studies have shown that structurally modified lopinavir, favipiravir, and other similar compounds can inhibit COVID-19 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp).	Lopinavir	46-55	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-178
33251975-9	2022	Molecular interaction analyses have displayed that lopinavir and favipiravir analogues interact with the active site residues of Mpro and RdRp, respectively.	Lopinavir	51-60	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	138-142
33251975-9	2022	Molecular interaction analyses have displayed that lopinavir and favipiravir analogues interact with the active site residues of Mpro and RdRp, respectively.	favipiravir	65-76	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	138-142
33252031-0	2022	Identification of naphthyridine and quinoline derivatives as potential Nsp16-Nsp10 inhibitors: a pharmacoinformatics study.	Naphthyridines	18-31	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	77-82
33252031-0	2022	Identification of naphthyridine and quinoline derivatives as potential Nsp16-Nsp10 inhibitors: a pharmacoinformatics study.	quinoline	36-45	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	77-82
33252031-3	2022	A set of 58 molecules belongs to the naphthyridine and quinoline derivatives have been recently synthesized and considered for structure-based virtual screening against Nsp16-Nsp10.	Naphthyridines	37-50	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	175-180
33252031-3	2022	A set of 58 molecules belongs to the naphthyridine and quinoline derivatives have been recently synthesized and considered for structure-based virtual screening against Nsp16-Nsp10.	quinoline	55-64	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	175-180
33252031-5	2022	Fourteen out of fifty-eight compounds were exhibited binding affinity higher than co-crystal bound ligand s-adenosylmethionine (SAM) toward Nsp16-Nsp10.	S-Adenosylmethionine	106-126	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	146-151
33252031-5	2022	Fourteen out of fifty-eight compounds were exhibited binding affinity higher than co-crystal bound ligand s-adenosylmethionine (SAM) toward Nsp16-Nsp10.	S-Adenosylmethionine	128-131	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	146-151
33335812-8	2020	The results reveal that two drugs, docetaxel and neohesperidin, showed strong binding profiles with SARS CoV-2 RdRP.	neohesperidin	49-62	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
32950529-5	2020	This study revealed that Rifabutin, Rifapentine, Fidaxomicin, 7-methyl-guanosine-5"-triphosphate-5"-guanosine and Ivermectin have a potential inhibitory interaction with RdRp of SARS-CoV-2, and could be effective drugs for COVID-19.	Rifabutin	25-34	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	170-174
32915473-0	2020	Gold Metallodrugs to Target Coronavirus Proteins: Inhibitory Effects on the Spike-ACE2 Interaction and on PLpro Protease Activity by Auranofin and Gold Organometallics*.	Auranofin	133-142	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	106-111
33330626-7	2020	We observed from our simulations that the presence of nsp10 increases the favorable van der Waals and electrostatic interactions between SAM and nsp16.	nsp16	145-150	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	54-59
33330626-10	2020	Also, the stable hydrogen bonds between Ala83 (nsp16) and Tyr96 (nsp10), and between Gln87 (nsp16) and Leu45 (nsp10) play a vital role in the dimerization of nsp16 and nsp10.	Hydrogen	17-25	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	65-70
33330626-10	2020	Also, the stable hydrogen bonds between Ala83 (nsp16) and Tyr96 (nsp10), and between Gln87 (nsp16) and Leu45 (nsp10) play a vital role in the dimerization of nsp16 and nsp10.	Hydrogen	17-25	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	110-115
33330626-10	2020	Also, the stable hydrogen bonds between Ala83 (nsp16) and Tyr96 (nsp10), and between Gln87 (nsp16) and Leu45 (nsp10) play a vital role in the dimerization of nsp16 and nsp10.	Hydrogen	17-25	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	110-115
32967965-2	2020	RDV targets the viral RNA-dependent RNA polymerase (RdRp) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).	remdesivir	0-3	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	52-56
32967965-4	2020	Here we demonstrate that the S861G mutation in RdRp eliminates chain termination, which confirms the existence of a steric clash between Ser-861 and the incorporated RDV-TP.	Serine	137-140	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	47-51
32967965-4	2020	Here we demonstrate that the S861G mutation in RdRp eliminates chain termination, which confirms the existence of a steric clash between Ser-861 and the incorporated RDV-TP.	remdesivir	166-169	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	47-51
32967965-5	2020	With WT RdRp, increasing concentrations of NTP pools cause a gradual decrease in termination and the resulting read-through increases full-length product formation.	ntp	43-46	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	8-12
32967965-11	2020	The collective data provide strong evidence to show that template-dependent inhibition of SARS-CoV-2 RdRp by RDV is biologically relevant.	remdesivir	109-112	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	101-105
32834110-0	2020	Azafluorene derivatives as inhibitors of SARS CoV-2 RdRp: Synthesis, physicochemical, quantum chemical, modeling and molecular docking analysis.	Azafluorene	0-11	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	52-56
33190493-0	2020	Revealing the Inhibition Mechanism of RNA-Dependent RNA Polymerase (RdRp) of SARS-CoV-2 by Remdesivir and Nucleotide Analogues: A Molecular Dynamics Simulation Study.	remdesivir	91-101	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	68-72
33190493-2	2020	Remdesivir is the first antiviral compound approved by the US FDA for the SARS-CoV-2 treatment for emergency use, targeting RNA-dependent RNA polymerase (RdRp) enzyme.	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	154-158
33190493-7	2020	The binding energy data reveal that compound-17 (-59.6 kcal/mol) binds more strongly as compared to compound-8 (-46.3 kcal/mol) and remdesivir (-29.7 kcal/mol) with RdRp.	remdesivir	132-142	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	165-169
33269349-1	2020	The SARS-CoV-2 macrodomain (Mac1) within the non-structural protein 3 (Nsp3) counteracts host-mediated antiviral ADP-ribosylation signalling.	Adenosine Diphosphate	113-116	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	71-75
33200683-0	2022	Computational investigation of binding of chloroquinone and hydroxychloroquinone against PLPro of SARS-CoV-2.	2-chloro-1,4-benzoquinone	42-55	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	89-94
33200683-0	2022	Computational investigation of binding of chloroquinone and hydroxychloroquinone against PLPro of SARS-CoV-2.	hydroxychloroquinone	60-80	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	89-94
33200683-6	2022	Inspired by this fact, we have carried out molecular docking and dynamics simulation studies of FDA approved CQ and HCQ against SARS-CoV-2 PLpro.	Chloroquine	109-111	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	139-144
33200683-6	2022	Inspired by this fact, we have carried out molecular docking and dynamics simulation studies of FDA approved CQ and HCQ against SARS-CoV-2 PLpro.	Hydroxychloroquine	116-119	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	139-144
33200683-9	2022	We showed that the CQ and HCQ can bind with better binding affinity with PLpro as compared to reference known PLpro inhibitor.	Chloroquine	19-21	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	73-78
33200683-9	2022	We showed that the CQ and HCQ can bind with better binding affinity with PLpro as compared to reference known PLpro inhibitor.	Chloroquine	19-21	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	110-115
33200683-9	2022	We showed that the CQ and HCQ can bind with better binding affinity with PLpro as compared to reference known PLpro inhibitor.	Hydroxychloroquine	26-29	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	73-78
33200683-9	2022	We showed that the CQ and HCQ can bind with better binding affinity with PLpro as compared to reference known PLpro inhibitor.	Hydroxychloroquine	26-29	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	110-115
33200683-10	2022	Based on the presented findings, it can be anticipated that the SARS-CoV-2 PLpro may act as molecular target of CQ and HCQ, and can be projected for further exploration to design potent inhibitors of SARS-CoV-2 PLpro in the near future.	Chloroquine	112-114	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	75-80
33200683-10	2022	Based on the presented findings, it can be anticipated that the SARS-CoV-2 PLpro may act as molecular target of CQ and HCQ, and can be projected for further exploration to design potent inhibitors of SARS-CoV-2 PLpro in the near future.	Chloroquine	112-114	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	211-216
33200683-10	2022	Based on the presented findings, it can be anticipated that the SARS-CoV-2 PLpro may act as molecular target of CQ and HCQ, and can be projected for further exploration to design potent inhibitors of SARS-CoV-2 PLpro in the near future.	Hydroxychloroquine	119-122	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	75-80
33201386-6	2021	Based on molecular dock scores, molecular interaction with active catalytic residues and molecular dynamics (MD) simulations studies, STOCK1N-69160 [(S)-2-((R)-4-((R)-2-amino-3-methylbutanamido)-3-(4-chlorophenyl) butanamido) propanoic acid hydrochloride] has been proposed as a novel inhibitor against COVID-19 PLpro.	stock1n-69160	134-147	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	312-317
32950529-6	2020	In addition, virtual screening of the compounds from ZINC database also allowed the prediction of two compounds (ZINC09128258 and ZINC09883305) with pharmacophore features that interact effectively with RdRp of SARS-CoV-2, indicating their potentiality as effective inhibitors of the enzyme.	zinc09883305	130-142	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	203-207
32950529-5	2020	This study revealed that Rifabutin, Rifapentine, Fidaxomicin, 7-methyl-guanosine-5"-triphosphate-5"-guanosine and Ivermectin have a potential inhibitory interaction with RdRp of SARS-CoV-2, and could be effective drugs for COVID-19.	rifapentine	36-47	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	170-174
32950529-5	2020	This study revealed that Rifabutin, Rifapentine, Fidaxomicin, 7-methyl-guanosine-5"-triphosphate-5"-guanosine and Ivermectin have a potential inhibitory interaction with RdRp of SARS-CoV-2, and could be effective drugs for COVID-19.	Fidaxomicin	49-60	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	170-174
32950529-5	2020	This study revealed that Rifabutin, Rifapentine, Fidaxomicin, 7-methyl-guanosine-5"-triphosphate-5"-guanosine and Ivermectin have a potential inhibitory interaction with RdRp of SARS-CoV-2, and could be effective drugs for COVID-19.	MRNA CAP ANALOG N7-METHYL GPPPG	62-109	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	170-174
32950529-5	2020	This study revealed that Rifabutin, Rifapentine, Fidaxomicin, 7-methyl-guanosine-5"-triphosphate-5"-guanosine and Ivermectin have a potential inhibitory interaction with RdRp of SARS-CoV-2, and could be effective drugs for COVID-19.	Ivermectin	114-124	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	170-174
33183178-6	2022	In this study, an antiviral drug- Remdesivir (RdRp inhibitor) and Darunavir (Mpro inhibitor) are used as reference drugs.	remdesivir	34-44	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	46-50
33183178-9	2022	Besides, to assess the stability, MD simulations studies were performed along with reference inhibitors for Mpro (Darunavir) and RdRp (Remdesivir).	remdesivir	135-145	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	129-133
32950529-6	2020	In addition, virtual screening of the compounds from ZINC database also allowed the prediction of two compounds (ZINC09128258 and ZINC09883305) with pharmacophore features that interact effectively with RdRp of SARS-CoV-2, indicating their potentiality as effective inhibitors of the enzyme.	zinc09128258	113-125	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	203-207
33183178-10	2022	Binding free energy calculations (MM-PBSA) revealed the estimated value (DeltaG) of Mpro_Darunavir; Mpro_Mulberroside E; RdRp_Remdesivir and RdRp_Emblicanin A were -111.62 +- 6.788, -141.443 +- 9.313, 30.782 +- 5.85 and -89.424 +- 3.130 kJmol-1, respectively.	remdesivir	126-136	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	121-125
33183178-7	2022	This study revealed that phyto-molecules- Mulberroside-A/C/E/F, Emblicanin A, Nimbolide, and Punigluconin showed high binding affinity against RdRp while Andrographolides, Mulberrosides, Anolignans, Chebulic acid, Mimusopic acid, and Punigluconin showed better binding affinity against Mpro as compared with the reference drug.	phyto-molecules- mulberroside	25-54	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
32692185-2	2020	On the basis of our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously demonstrated that three nucleotide analogues (the triphosphates of Sofosbuvir, Alovudine, and AZT) inhibit the SARS-CoV RNA-dependent RNA polymerase (RdRp).	triphosphoric acid	208-221	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	308-312
33183178-7	2022	This study revealed that phyto-molecules- Mulberroside-A/C/E/F, Emblicanin A, Nimbolide, and Punigluconin showed high binding affinity against RdRp while Andrographolides, Mulberrosides, Anolignans, Chebulic acid, Mimusopic acid, and Punigluconin showed better binding affinity against Mpro as compared with the reference drug.	emblicanin A	64-76	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33183178-7	2022	This study revealed that phyto-molecules- Mulberroside-A/C/E/F, Emblicanin A, Nimbolide, and Punigluconin showed high binding affinity against RdRp while Andrographolides, Mulberrosides, Anolignans, Chebulic acid, Mimusopic acid, and Punigluconin showed better binding affinity against Mpro as compared with the reference drug.	nimbolide	78-87	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33183178-7	2022	This study revealed that phyto-molecules- Mulberroside-A/C/E/F, Emblicanin A, Nimbolide, and Punigluconin showed high binding affinity against RdRp while Andrographolides, Mulberrosides, Anolignans, Chebulic acid, Mimusopic acid, and Punigluconin showed better binding affinity against Mpro as compared with the reference drug.	Punigluconin	93-105	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33183178-7	2022	This study revealed that phyto-molecules- Mulberroside-A/C/E/F, Emblicanin A, Nimbolide, and Punigluconin showed high binding affinity against RdRp while Andrographolides, Mulberrosides, Anolignans, Chebulic acid, Mimusopic acid, and Punigluconin showed better binding affinity against Mpro as compared with the reference drug.	anolignans	187-197	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33183178-7	2022	This study revealed that phyto-molecules- Mulberroside-A/C/E/F, Emblicanin A, Nimbolide, and Punigluconin showed high binding affinity against RdRp while Andrographolides, Mulberrosides, Anolignans, Chebulic acid, Mimusopic acid, and Punigluconin showed better binding affinity against Mpro as compared with the reference drug.	chebulic acid	199-212	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33183178-7	2022	This study revealed that phyto-molecules- Mulberroside-A/C/E/F, Emblicanin A, Nimbolide, and Punigluconin showed high binding affinity against RdRp while Andrographolides, Mulberrosides, Anolignans, Chebulic acid, Mimusopic acid, and Punigluconin showed better binding affinity against Mpro as compared with the reference drug.	Mimuscopic acid	214-228	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33183178-7	2022	This study revealed that phyto-molecules- Mulberroside-A/C/E/F, Emblicanin A, Nimbolide, and Punigluconin showed high binding affinity against RdRp while Andrographolides, Mulberrosides, Anolignans, Chebulic acid, Mimusopic acid, and Punigluconin showed better binding affinity against Mpro as compared with the reference drug.	Punigluconin	234-246	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33176643-8	2021	RESULTS: Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro SARS-CoV-2 as evident from molecular docking study which was found to be even better than remdesivir (-6.1 Kcal/mol), chloroquine (-5.3 Kcal/mol) and favipiravir (-5.7 Kcal/mol).	NIMBOCINOL	9-19	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-95
33176643-8	2021	RESULTS: Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro SARS-CoV-2 as evident from molecular docking study which was found to be even better than remdesivir (-6.1 Kcal/mol), chloroquine (-5.3 Kcal/mol) and favipiravir (-5.7 Kcal/mol).	Barium	79-81	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-95
33176643-8	2021	RESULTS: Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro SARS-CoV-2 as evident from molecular docking study which was found to be even better than remdesivir (-6.1 Kcal/mol), chloroquine (-5.3 Kcal/mol) and favipiravir (-5.7 Kcal/mol).	remdesivir	186-196	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-95
33176643-8	2021	RESULTS: Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro SARS-CoV-2 as evident from molecular docking study which was found to be even better than remdesivir (-6.1 Kcal/mol), chloroquine (-5.3 Kcal/mol) and favipiravir (-5.7 Kcal/mol).	Chloroquine	214-225	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-95
33176643-8	2021	RESULTS: Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro SARS-CoV-2 as evident from molecular docking study which was found to be even better than remdesivir (-6.1 Kcal/mol), chloroquine (-5.3 Kcal/mol) and favipiravir (-5.7 Kcal/mol).	favipiravir	246-257	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-95
33176643-9	2021	Both nimbocinol-PLpro and sage-PLpro SARS-CoV-2 complex exhibited stable conformation during MD Simulation of 101ns at 310 K and potential, kinetic and electrostatic interaction energies were computed which was observed to be concordant with results of molecular docking study.	NIMBOCINOL	5-15	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	16-21
33176643-9	2021	Both nimbocinol-PLpro and sage-PLpro SARS-CoV-2 complex exhibited stable conformation during MD Simulation of 101ns at 310 K and potential, kinetic and electrostatic interaction energies were computed which was observed to be concordant with results of molecular docking study.	NIMBOCINOL	5-15	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	31-36
33155531-5	2022	We successfully identified novel lead molecule such as Alectinib for RdRp while Naldemedine and Ergotamine for NSP15.	alectinib	55-64	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	69-73
32907334-6	2020	Additionally, we found a strong interaction between toremifene and the methyltransferase non-structural protein (NSP) 14, which could be inhibitory to viral replication via its active site.	Toremifene	52-62	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	113-116
32692185-4	2020	Here, we used polymerase extension experiments to demonstrate that the active triphosphate form of Sofosbuvir (an FDA-approved hepatitis C drug) is incorporated by SARS-CoV-2 RdRp and blocks further incorporation.	triphosphoric acid	78-90	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	175-179
32692185-4	2020	Here, we used polymerase extension experiments to demonstrate that the active triphosphate form of Sofosbuvir (an FDA-approved hepatitis C drug) is incorporated by SARS-CoV-2 RdRp and blocks further incorporation.	Sofosbuvir	99-109	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	175-179
32692185-5	2020	Using the molecular insight gained from the previous studies, we selected the active triphosphate forms of six other antiviral agents, Alovudine, Tenofovir alafenamide, AZT, Abacavir, Lamivudine, and Emtricitabine, for evaluation as inhibitors of the SARS-CoV-2 RdRp and demonstrated the ability of these viral polymerase inhibitors to be incorporated by SARS-CoV-2 RdRp, where they terminate further polymerase extension with varying efficiency.	triphosphoric acid	85-97	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	262-266
32692185-5	2020	Using the molecular insight gained from the previous studies, we selected the active triphosphate forms of six other antiviral agents, Alovudine, Tenofovir alafenamide, AZT, Abacavir, Lamivudine, and Emtricitabine, for evaluation as inhibitors of the SARS-CoV-2 RdRp and demonstrated the ability of these viral polymerase inhibitors to be incorporated by SARS-CoV-2 RdRp, where they terminate further polymerase extension with varying efficiency.	triphosphoric acid	85-97	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	366-370
32712315-10	2020	Although Cys-rich derived CPPs of helicase (NSP13) can potentially fold into a cyclic conformation in endosomes with a higher rate of endosomal release, the most optimal SCV2-CPP candidates as vectors for drug delivery were SCV2-CPP118, SCV2-CPP119, SCV2-CPP122, and SCV2-CPP129 of NSP12 (RdRp).	Cysteine	9-12	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	289-293
32947136-4	2020	Remdesivir, an RdRp inhibitor, exhibited potent activity against SARS-CoV-2 in vitro.	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	15-19
33230487-5	2020	The aim of this present work deals with the potential binding interactions of some imidazolium salts with Nsp9 (Nonstructural protein 9) RNA binding protein of SARS CoV-2.	imidazolium salts	83-100	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	106-110
33251371-0	2020	Structure-based drug designing of naphthalene based SARS-CoV PLpro inhibitors for the treatment of COVID-19.	naphthalene	34-45	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	61-66
33251371-4	2020	In the current investigation, an attempt was made to design potential SARS-CoV PLpro inhibitors containing naphthalene and 3,4-dihydro-2H-pyran moieties connected via -NHCO- linker.	naphthalene	107-118	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	79-84
32535456-4	2020	This study revealed that Protopine, Allocryptopine and (+-) 6- Acetonyldihydrochelerythrine could be potential RdRp inhibitors of SARS-CoV-2.	protopine	25-34	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
33251371-4	2020	In the current investigation, an attempt was made to design potential SARS-CoV PLpro inhibitors containing naphthalene and 3,4-dihydro-2H-pyran moieties connected via -NHCO- linker.	3,4-dihydro-(2H)-pyran	123-143	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	79-84
32535456-4	2020	This study revealed that Protopine, Allocryptopine and (+-) 6- Acetonyldihydrochelerythrine could be potential RdRp inhibitors of SARS-CoV-2.	allocryptopine	36-50	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
32535456-4	2020	This study revealed that Protopine, Allocryptopine and (+-) 6- Acetonyldihydrochelerythrine could be potential RdRp inhibitors of SARS-CoV-2.	6-acetonyldihydrochelerythrine	60-91	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
33100032-0	2020	Exploring RdRp-remdesivir interactions to screen RdRp inhibitors for the management of novel coronavirus 2019-nCoV.	remdesivir	15-25	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	10-14
33100032-0	2020	Exploring RdRp-remdesivir interactions to screen RdRp inhibitors for the management of novel coronavirus 2019-nCoV.	remdesivir	15-25	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	49-53
33100032-5	2020	Therefore, in the current work, the authors have attempted to utilize the remdesivir-RdRp complex - RdRp (RNA-dependent RNA polymerase) being the putative target for remdesivir - to screen a library of the already reported RdRp inhibitor database.	remdesivir	74-84	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	85-89
33100032-5	2020	Therefore, in the current work, the authors have attempted to utilize the remdesivir-RdRp complex - RdRp (RNA-dependent RNA polymerase) being the putative target for remdesivir - to screen a library of the already reported RdRp inhibitor database.	remdesivir	74-84	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	100-104
33100032-5	2020	Therefore, in the current work, the authors have attempted to utilize the remdesivir-RdRp complex - RdRp (RNA-dependent RNA polymerase) being the putative target for remdesivir - to screen a library of the already reported RdRp inhibitor database.	remdesivir	74-84	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	100-104
33100032-5	2020	Therefore, in the current work, the authors have attempted to utilize the remdesivir-RdRp complex - RdRp (RNA-dependent RNA polymerase) being the putative target for remdesivir - to screen a library of the already reported RdRp inhibitor database.	remdesivir	166-176	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	85-89
33100032-5	2020	Therefore, in the current work, the authors have attempted to utilize the remdesivir-RdRp complex - RdRp (RNA-dependent RNA polymerase) being the putative target for remdesivir - to screen a library of the already reported RdRp inhibitor database.	remdesivir	166-176	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	100-104
33100032-5	2020	Therefore, in the current work, the authors have attempted to utilize the remdesivir-RdRp complex - RdRp (RNA-dependent RNA polymerase) being the putative target for remdesivir - to screen a library of the already reported RdRp inhibitor database.	remdesivir	166-176	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	100-104
33100032-8	2020	The results yielded two putative hits which can inhibit RdRp with better potency than remdesivir, subject to further biological evaluation.	remdesivir	86-96	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	56-60
33089730-10	2022	Out of 32 phytochemicals, amentoflavone and gallocatechin gallate showed the best binding affinity to 3CLpro (-9.4 kcal/mol) and PLpro (-8.8 kcal/mol).	amentoflavone	26-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	129-134
33089730-10	2022	Out of 32 phytochemicals, amentoflavone and gallocatechin gallate showed the best binding affinity to 3CLpro (-9.4 kcal/mol) and PLpro (-8.8 kcal/mol).	gallocatechin gallate	44-65	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	129-134
33089730-15	2022	The present study thus suggests that Amentoflavone and Gallocatechin gallate may be potential inhibitors of 3CLpro and PLpro proteins and effective drug candidates for SARS-CoV2.	amentoflavone	37-50	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	119-124
33089730-15	2022	The present study thus suggests that Amentoflavone and Gallocatechin gallate may be potential inhibitors of 3CLpro and PLpro proteins and effective drug candidates for SARS-CoV2.	gallocatechin gallate	55-76	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	119-124
33076559-7	2020	In addition, we describe base pairs that target the RNA-dependent RNA polymerase (RdRp) of RNA viruses and describe implications for the 2019 novel coronavirus (SARS-CoV-2): When products of oxidative guanine damage are adapted for the ribonucleoside analogs, mimics of oxidative guanine damages, which can form base pairs, may become antiviral agents for SARS-CoV-2.	Guanine	201-208	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	82-86
32702590-3	2020	In this study, referencing the data published on the Protein Data Bank (PDB ID: 7BV2) on April 22, we conducted a detailed analysis of the interaction between the complex structures of the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and Remdesivir, an antiviral drug, from the quantum chemical perspective based on the fragment molecular orbital (FMO) method.	remdesivir	243-253	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	219-223
33084512-7	2022	Computational analyses revealed that the interaction with hesperidin (theoretical binding energies, DeltaGbind = -15.18 kcal/mol to 3CLpro and DeltaGbind = -9.46 kcal/mol to RdRp) remained stable in both enzymes, unveiling its remarkable potential as a possible multitarget antiviral agent to treat COVID-19.	Hesperidin	58-68	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-178
33076559-7	2020	In addition, we describe base pairs that target the RNA-dependent RNA polymerase (RdRp) of RNA viruses and describe implications for the 2019 novel coronavirus (SARS-CoV-2): When products of oxidative guanine damage are adapted for the ribonucleoside analogs, mimics of oxidative guanine damages, which can form base pairs, may become antiviral agents for SARS-CoV-2.	Guanine	280-287	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	82-86
33027419-0	2020	Flavonoid glycosides and their putative human metabolites as potential inhibitors of the SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp).	Flavonoids	0-9	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	155-159
33014317-5	2020	Methods: Using some docking methods, RdRP was targeted by Milbemycins (MMs), Ivermectin (IMT), Baloxavir Marboxil (BM), and Tadalafil (TF), a phosphodiesterase type 5 inhibitor.	moxidectin	58-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	37-41
33014317-5	2020	Methods: Using some docking methods, RdRP was targeted by Milbemycins (MMs), Ivermectin (IMT), Baloxavir Marboxil (BM), and Tadalafil (TF), a phosphodiesterase type 5 inhibitor.	moxidectin	71-74	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	37-41
33014317-5	2020	Methods: Using some docking methods, RdRP was targeted by Milbemycins (MMs), Ivermectin (IMT), Baloxavir Marboxil (BM), and Tadalafil (TF), a phosphodiesterase type 5 inhibitor.	Ivermectin	77-87	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	37-41
33014317-5	2020	Methods: Using some docking methods, RdRP was targeted by Milbemycins (MMs), Ivermectin (IMT), Baloxavir Marboxil (BM), and Tadalafil (TF), a phosphodiesterase type 5 inhibitor.	baloxavir	95-113	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	37-41
33014317-5	2020	Methods: Using some docking methods, RdRP was targeted by Milbemycins (MMs), Ivermectin (IMT), Baloxavir Marboxil (BM), and Tadalafil (TF), a phosphodiesterase type 5 inhibitor.	baloxavir	115-117	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	37-41
33014317-5	2020	Methods: Using some docking methods, RdRP was targeted by Milbemycins (MMs), Ivermectin (IMT), Baloxavir Marboxil (BM), and Tadalafil (TF), a phosphodiesterase type 5 inhibitor.	Tadalafil	124-133	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	37-41
33014317-6	2020	Results: MM-A3 5-oxime (MMA35O), MM-A3 (MMA3), MM-A4 5-oxime (MMA45O), IMT, BM, and TF showed the highest binding affinity to RdRp.	mm-a3 5-oxime	9-22	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-130
33014317-6	2020	Results: MM-A3 5-oxime (MMA35O), MM-A3 (MMA3), MM-A4 5-oxime (MMA45O), IMT, BM, and TF showed the highest binding affinity to RdRp.	mma35o	24-30	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-130
33014317-6	2020	Results: MM-A3 5-oxime (MMA35O), MM-A3 (MMA3), MM-A4 5-oxime (MMA45O), IMT, BM, and TF showed the highest binding affinity to RdRp.	moxidectin	9-14	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-130
33014317-6	2020	Results: MM-A3 5-oxime (MMA35O), MM-A3 (MMA3), MM-A4 5-oxime (MMA45O), IMT, BM, and TF showed the highest binding affinity to RdRp.	mm-a4 5-oxime	47-60	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-130
33014317-7	2020	Conclusion: The drugs used in the present computational investigation are effective against the SARS-CoV-2 RdRP with high affinity values especially, milbemycins, ivermectin, and Baloxavir marboxil, which could further be studied in laboratory and clinical trials for saving millions of lives around the world.	moxidectin	150-161	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	107-111
33014317-7	2020	Conclusion: The drugs used in the present computational investigation are effective against the SARS-CoV-2 RdRP with high affinity values especially, milbemycins, ivermectin, and Baloxavir marboxil, which could further be studied in laboratory and clinical trials for saving millions of lives around the world.	Ivermectin	163-173	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	107-111
33014317-7	2020	Conclusion: The drugs used in the present computational investigation are effective against the SARS-CoV-2 RdRP with high affinity values especially, milbemycins, ivermectin, and Baloxavir marboxil, which could further be studied in laboratory and clinical trials for saving millions of lives around the world.	baloxavir	179-197	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	107-111
32505692-8	2020	Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed.	Oligonucleotides	60-76	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	91-95
32812340-9	2020	It is, therefore, possible that methylcobalamin binding may prevent association with RNA and NTP and thus inhibit the RdRP activity of nsp12.	mecobalamin	32-47	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	118-122
33027419-5	2020	FINDINGS: Docking analysis, based on the crystal structure of 3CLpro and RdRp, indicated rutin, nicotiflorin, and their glucuronide and sulfate derivatives as potential inhibitors for both proteins.	Glucuronides	120-131	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	73-77
33027419-7	2020	MAIN CONCLUSIONS: Overall, these results suggest that both flavonoid glycosides and their putative human metabolites can play a key role as inhibitors of the SARS-CoV-2 3CLpro and RdRp.	flavonoid glycosides	59-79	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	180-184
33027419-0	2020	Flavonoid glycosides and their putative human metabolites as potential inhibitors of the SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp).	Glycosides	10-20	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	155-159
33027419-3	2020	OBJECTIVES: To investigate, in silico, two of the most abundant flavonoid glycosides from Dysphania ambrosioides; a medicinal plant found in many regions of the world, along with some of the putative derivatives of these flavonoid glycosides in the human organism as potential inhibitors of the SARS-CoV-2 3CLpro and RdRp.	flavonoid glycosides	64-84	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	317-321
33027419-4	2020	METHODS: Using a molecular docking approach, the interactions and the binding affinity with SARS-CoV-2 3CLpro and RdRp were predicted for quercetin-3-O-rutinoside (rutin), kaempferol-3-O-rutinoside (nicotiflorin) and some of their glucuronide and sulfate derivatives.	quercetin-3-O-rutinoside	138-162	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	114-118
33027419-4	2020	METHODS: Using a molecular docking approach, the interactions and the binding affinity with SARS-CoV-2 3CLpro and RdRp were predicted for quercetin-3-O-rutinoside (rutin), kaempferol-3-O-rutinoside (nicotiflorin) and some of their glucuronide and sulfate derivatives.	quercetin-3-O-rutinoside	152-157	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	114-118
33027419-4	2020	METHODS: Using a molecular docking approach, the interactions and the binding affinity with SARS-CoV-2 3CLpro and RdRp were predicted for quercetin-3-O-rutinoside (rutin), kaempferol-3-O-rutinoside (nicotiflorin) and some of their glucuronide and sulfate derivatives.	kaempferol-3-O-rutinoside	172-197	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	114-118
33027419-4	2020	METHODS: Using a molecular docking approach, the interactions and the binding affinity with SARS-CoV-2 3CLpro and RdRp were predicted for quercetin-3-O-rutinoside (rutin), kaempferol-3-O-rutinoside (nicotiflorin) and some of their glucuronide and sulfate derivatives.	nicotiflorin	199-211	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	114-118
33027419-4	2020	METHODS: Using a molecular docking approach, the interactions and the binding affinity with SARS-CoV-2 3CLpro and RdRp were predicted for quercetin-3-O-rutinoside (rutin), kaempferol-3-O-rutinoside (nicotiflorin) and some of their glucuronide and sulfate derivatives.	Glucuronides	231-242	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	114-118
33027419-4	2020	METHODS: Using a molecular docking approach, the interactions and the binding affinity with SARS-CoV-2 3CLpro and RdRp were predicted for quercetin-3-O-rutinoside (rutin), kaempferol-3-O-rutinoside (nicotiflorin) and some of their glucuronide and sulfate derivatives.	Sulfates	247-254	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	114-118
33027419-5	2020	FINDINGS: Docking analysis, based on the crystal structure of 3CLpro and RdRp, indicated rutin, nicotiflorin, and their glucuronide and sulfate derivatives as potential inhibitors for both proteins.	nicotiflorin	96-108	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	73-77
32943628-6	2020	The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.	Nucleosides	82-92	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	16-20
33072018-7	2020	A strong bias in nucleotide usage in fourfold degenerate sites toward uracil residues is seen in ORF1ab of all the studied coronaviruses: both in the ORF1a and in the ORF1b translated thanks to the programmed ribosomal frameshifting that has an efficiency of 14 - 45% in different species.	Uracil	70-76	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	97-103
32994211-3	2020	We determined the structures for nsp16-nsp10 heterodimers bound to the methyl donor S-adenosylmethionine (SAM), the reaction product S-adenosylhomocysteine (SAH), or the SAH analog sinefungin (SFG).	S-Adenosylmethionine	84-104	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	39-44
32994211-3	2020	We determined the structures for nsp16-nsp10 heterodimers bound to the methyl donor S-adenosylmethionine (SAM), the reaction product S-adenosylhomocysteine (SAH), or the SAH analog sinefungin (SFG).	S-Adenosylmethionine	106-109	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	39-44
32994211-3	2020	We determined the structures for nsp16-nsp10 heterodimers bound to the methyl donor S-adenosylmethionine (SAM), the reaction product S-adenosylhomocysteine (SAH), or the SAH analog sinefungin (SFG).	S-Adenosylhomocysteine	133-155	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	39-44
32994211-3	2020	We determined the structures for nsp16-nsp10 heterodimers bound to the methyl donor S-adenosylmethionine (SAM), the reaction product S-adenosylhomocysteine (SAH), or the SAH analog sinefungin (SFG).	sinefungin	181-191	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	39-44
32994211-3	2020	We determined the structures for nsp16-nsp10 heterodimers bound to the methyl donor S-adenosylmethionine (SAM), the reaction product S-adenosylhomocysteine (SAH), or the SAH analog sinefungin (SFG).	sinefungin	193-196	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	39-44
32994211-4	2020	We also solved structures for nsp16-nsp10 in complex with the methylated Cap-0 analog m7GpppA and either SAM or SAH.	m7GpppA	86-93	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	36-41
32783916-9	2020	We also observe ADP-Mg2+ bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapy development.	Adenosine Diphosphate	16-19	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	65-69
32783916-9	2020	We also observe ADP-Mg2+ bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapy development.	magnesium ion	20-24	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	65-69
33824130-12	2020	We have checked Thymoquinone as ligand for various targets of 2019-nCoV (receptor binding domain of spike, RNA polymerase, protease, Nsp9 RNA binding protein, nucleocapsid phosphoprotein, endoribonuclease) by protein-ligand docking server SwissDoc.	thymoquinone	16-28	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	133-137
32563812-1	2020	Remdesivir (GS-5734), a viral RNA-dependent RNA polymerase (RdRP) inhibitor that can be used to treat a variety of RNA virus infections, is expected to be an effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	60-64
32887884-4	2020	Moreover, combined application of GC376 with Remdesivir, a nucleotide analogue that inhibits viral RNA dependent RNA polymerase (RdRp), results in sterilizing additive effect.	remdesivir	45-55	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	129-133
32521159-3	2020	Here, we used molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp).	remdesivir	119-129	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	191-195
32835632-0	2021	In silico validation of coumarin derivatives as potential inhibitors against Main Protease, NSP10/NSP16-Methyltransferase, Phosphatase and Endoribonuclease of SARS CoV-2.	coumarin	24-32	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	92-97
32428392-7	2020	Additionally, naphthalene based PLpro inhibitors are shown to be effective at halting SARS-CoV-2 PLpro activity as well as SARS-CoV-2 replication.	naphthalene	14-25	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	32-37
32428392-7	2020	Additionally, naphthalene based PLpro inhibitors are shown to be effective at halting SARS-CoV-2 PLpro activity as well as SARS-CoV-2 replication.	naphthalene	14-25	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	97-102
32824072-4	2020	Furthermore, CQ and HCQ also influenced the proofreading and capping of viral RNA in SARS-CoV-2, performed by nsp10/nsp14 and nsp10/nsp16.	Chloroquine	13-15	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	110-115
32824072-4	2020	Furthermore, CQ and HCQ also influenced the proofreading and capping of viral RNA in SARS-CoV-2, performed by nsp10/nsp14 and nsp10/nsp16.	Chloroquine	13-15	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-131
32824072-4	2020	Furthermore, CQ and HCQ also influenced the proofreading and capping of viral RNA in SARS-CoV-2, performed by nsp10/nsp14 and nsp10/nsp16.	Hydroxychloroquine	20-23	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	110-115
32824072-4	2020	Furthermore, CQ and HCQ also influenced the proofreading and capping of viral RNA in SARS-CoV-2, performed by nsp10/nsp14 and nsp10/nsp16.	Hydroxychloroquine	20-23	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-131
32521159-9	2020	The ~100-fold improvement in the Kd from remdesivir over ATP indicates an effective replacement of ATP in blocking of the RdRp preinsertion site.	remdesivir	41-51	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	122-126
32521159-9	2020	The ~100-fold improvement in the Kd from remdesivir over ATP indicates an effective replacement of ATP in blocking of the RdRp preinsertion site.	Adenosine Triphosphate	57-60	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	122-126
32521159-9	2020	The ~100-fold improvement in the Kd from remdesivir over ATP indicates an effective replacement of ATP in blocking of the RdRp preinsertion site.	Adenosine Triphosphate	99-102	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	122-126
32521159-5	2020	We then built a putative preinsertion binding structure by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp without the RNA template.	remdesivir	72-82	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	85-89
32521159-5	2020	We then built a putative preinsertion binding structure by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp without the RNA template.	remdesivir	72-82	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-130
32521159-5	2020	We then built a putative preinsertion binding structure by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp without the RNA template.	Adenosine Triphosphate	105-108	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-130
32521159-7	2020	The resulting stable preinsertion state of remdesivir appeared to form hydrogen bonds with the RNA template when aligned with the newly solved cryo-EM structure of SARS-CoV-2 RdRp.	remdesivir	43-53	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	175-179
32521159-8	2020	The relative binding free energy between remdesivir and ATP was calculated to be -2.80 +- 0.84 kcal/mol, where remdesivir bound much stronger to SARS-CoV-2 RdRp than the natural substrate ATP.	remdesivir	41-51	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	156-160
32521159-8	2020	The relative binding free energy between remdesivir and ATP was calculated to be -2.80 +- 0.84 kcal/mol, where remdesivir bound much stronger to SARS-CoV-2 RdRp than the natural substrate ATP.	Adenosine Triphosphate	56-59	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	156-160
32521159-8	2020	The relative binding free energy between remdesivir and ATP was calculated to be -2.80 +- 0.84 kcal/mol, where remdesivir bound much stronger to SARS-CoV-2 RdRp than the natural substrate ATP.	remdesivir	111-121	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	156-160
32752938-7	2021	Similar analysis with RdRp showed that eltrombopag, tipranavir, ergotamine, and conivaptan bound to the enzyme with high binding free energies.	eltrombopag	39-50	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	22-26
32783586-5	2021	The RNA dependent RNA polymerase (RdRp) protein was selected as the target protein as favipiravir inhibits this protein in the human body.	favipiravir	86-97	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	34-38
32783586-7	2021	Then, the inhibition properties of selected drug candidates and favipiravir were examined in detail against SARS-CoV-2 RdRp proteins.	favipiravir	64-75	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	119-123
32821086-10	2020	The nucleoside analog inhibits the viral RNA-dependent RNA polymerase (RdRp) by competing with the usual counterpart adenosine triphosphate (ATP).	Nucleosides	4-14	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	71-75
32821086-10	2020	The nucleoside analog inhibits the viral RNA-dependent RNA polymerase (RdRp) by competing with the usual counterpart adenosine triphosphate (ATP).	Adenosine	117-126	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	71-75
32821086-10	2020	The nucleoside analog inhibits the viral RNA-dependent RNA polymerase (RdRp) by competing with the usual counterpart adenosine triphosphate (ATP).	Adenosine Triphosphate	141-144	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	71-75
32752938-7	2021	Similar analysis with RdRp showed that eltrombopag, tipranavir, ergotamine, and conivaptan bound to the enzyme with high binding free energies.	tipranavir	52-62	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	22-26
32633733-1	2020	Using a combination of enhanced sampling molecular dynamics techniques and non-equilibrium alchemical transformations with full atomistic details, we have shown that hydroxychloroquine (HCQ) may act as a mild inhibitor of important functional proteins for SARS-CoV2 replication, with potency increasing in the series PLpro, 3CLpro, RdRp.	Hydroxychloroquine	166-184	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	317-322
32633733-1	2020	Using a combination of enhanced sampling molecular dynamics techniques and non-equilibrium alchemical transformations with full atomistic details, we have shown that hydroxychloroquine (HCQ) may act as a mild inhibitor of important functional proteins for SARS-CoV2 replication, with potency increasing in the series PLpro, 3CLpro, RdRp.	Hydroxychloroquine	166-184	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	332-336
32752938-7	2021	Similar analysis with RdRp showed that eltrombopag, tipranavir, ergotamine, and conivaptan bound to the enzyme with high binding free energies.	Ergotamine	64-74	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	22-26
32633733-1	2020	Using a combination of enhanced sampling molecular dynamics techniques and non-equilibrium alchemical transformations with full atomistic details, we have shown that hydroxychloroquine (HCQ) may act as a mild inhibitor of important functional proteins for SARS-CoV2 replication, with potency increasing in the series PLpro, 3CLpro, RdRp.	Hydroxychloroquine	186-189	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	317-322
32633733-1	2020	Using a combination of enhanced sampling molecular dynamics techniques and non-equilibrium alchemical transformations with full atomistic details, we have shown that hydroxychloroquine (HCQ) may act as a mild inhibitor of important functional proteins for SARS-CoV2 replication, with potency increasing in the series PLpro, 3CLpro, RdRp.	Hydroxychloroquine	186-189	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	332-336
32752938-7	2021	Similar analysis with RdRp showed that eltrombopag, tipranavir, ergotamine, and conivaptan bound to the enzyme with high binding free energies.	conivaptan	80-90	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	22-26
32387040-5	2020	Coronaviruses are a family of positive-strand RNA viruses with conserved polymerase, so SARS-CoV-2 RdRp is very likely to be effectively inhibited by sofosbuvir.	Sofosbuvir	150-160	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-103
32850963-7	2020	We found that the naphthalene-based ligand shows strong potential as an inhibitor of CoV2 PLpro by binding at the putative naphthalene inhibitor binding site in both computational predictions and experimental assays.	naphthalene	18-29	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-95
32850963-7	2020	We found that the naphthalene-based ligand shows strong potential as an inhibitor of CoV2 PLpro by binding at the putative naphthalene inhibitor binding site in both computational predictions and experimental assays.	naphthalene	123-134	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-95
32850963-9	2020	The other ligand, chemotherapy drug 6-mercaptopurine (6MP), showed little to no stable intermolecular interaction with PLpro and quickly dissociated or remained highly mobile.	Mercaptopurine	36-52	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	119-124
32850963-9	2020	The other ligand, chemotherapy drug 6-mercaptopurine (6MP), showed little to no stable intermolecular interaction with PLpro and quickly dissociated or remained highly mobile.	Mercaptopurine	54-57	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	119-124
32562705-2	2020	We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir alafenamide and Emtricitabine.	triphosphoric acid	139-151	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
32562705-2	2020	We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir alafenamide and Emtricitabine.	Sofosbuvir	161-171	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
32562705-2	2020	We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir alafenamide and Emtricitabine.	Zidovudine	184-194	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
32562705-2	2020	We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir alafenamide and Emtricitabine.	tenofovir alafenamide	196-217	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
32562705-2	2020	We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir alafenamide and Emtricitabine.	Emtricitabine	222-235	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
32246834-4	2020	Favipiravir, a purine nucleic acid analog and potent RdRp inhibitor approved for use in influenza, is also considered in several clinical trials.	favipiravir	0-11	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	53-57
33062954-1	2020	SARS-CoV-2 encoded papain-like protease (PLpro) harbors a labile Zn site (Cys189-X-X-Cys192-X n -Cys224-X-Cys226) and a classic catalytic site (Cys111-His272-Asp286), which play key roles for viral replication and hence represent promising drug targets.	Zinc	65-67	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	41-46
33062954-2	2020	In this Viewpoint, both sulfur-based drugs and peptides-based inhibitors may block Cys residues in the catalytic and/or Zn site of CoV-2-PLpro, leading to dysfunction of CoV-2-PLpro and thereby halting viral replication.	Sulfur	24-30	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	137-142
33062954-2	2020	In this Viewpoint, both sulfur-based drugs and peptides-based inhibitors may block Cys residues in the catalytic and/or Zn site of CoV-2-PLpro, leading to dysfunction of CoV-2-PLpro and thereby halting viral replication.	Sulfur	24-30	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	176-181
33062954-2	2020	In this Viewpoint, both sulfur-based drugs and peptides-based inhibitors may block Cys residues in the catalytic and/or Zn site of CoV-2-PLpro, leading to dysfunction of CoV-2-PLpro and thereby halting viral replication.	Peptides	47-55	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	137-142
33062954-2	2020	In this Viewpoint, both sulfur-based drugs and peptides-based inhibitors may block Cys residues in the catalytic and/or Zn site of CoV-2-PLpro, leading to dysfunction of CoV-2-PLpro and thereby halting viral replication.	Peptides	47-55	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	176-181
33062954-2	2020	In this Viewpoint, both sulfur-based drugs and peptides-based inhibitors may block Cys residues in the catalytic and/or Zn site of CoV-2-PLpro, leading to dysfunction of CoV-2-PLpro and thereby halting viral replication.	Cysteine	83-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	137-142
33062954-2	2020	In this Viewpoint, both sulfur-based drugs and peptides-based inhibitors may block Cys residues in the catalytic and/or Zn site of CoV-2-PLpro, leading to dysfunction of CoV-2-PLpro and thereby halting viral replication.	Cysteine	83-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	176-181
33062954-2	2020	In this Viewpoint, both sulfur-based drugs and peptides-based inhibitors may block Cys residues in the catalytic and/or Zn site of CoV-2-PLpro, leading to dysfunction of CoV-2-PLpro and thereby halting viral replication.	Zinc	120-122	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	137-142
32709886-3	2020	We report here the high-resolution structure of a ternary complex of SARS-CoV-2 nsp16 and nsp10 in the presence of cognate RNA substrate analogue and methyl donor, S-adenosyl methionine (SAM).	S-Adenosylmethionine	164-185	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-95
32729392-4	2021	Molecular docking on 40 derivatives of standard drugs (Remdesivir, Lopinavir and Theophylline) led to the identification of R10, R2 and L9 as potential inhibitors of 3CLpro, PLpro and Spike protein, respectively.	remdesivir	55-65	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-179
32729392-4	2021	Molecular docking on 40 derivatives of standard drugs (Remdesivir, Lopinavir and Theophylline) led to the identification of R10, R2 and L9 as potential inhibitors of 3CLpro, PLpro and Spike protein, respectively.	Lopinavir	67-76	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-179
32729392-4	2021	Molecular docking on 40 derivatives of standard drugs (Remdesivir, Lopinavir and Theophylline) led to the identification of R10, R2 and L9 as potential inhibitors of 3CLpro, PLpro and Spike protein, respectively.	Theophylline	81-93	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-179
32720577-11	2021	Further, a 150-ns molecular dynamic simulation revealed that EGCG, TF2a, TF2b, TF3 result in highly stable bound conformations with RdRp.	epigallocatechin gallate	61-65	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	132-136
32720577-14	2021	Overall, our results suggest that EGCG, TF2a, TF2b, TF3 can inhibit RdRp and represent an effective therapy for COVID-19.	epigallocatechin gallate	34-38	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	68-72
32718300-0	2021	In Silico Identification of a Potent Arsenic Based Approved Drug Darinaparsin against SARS-CoV-2: Inhibitor of RNA Dependent RNA polymerase (RdRp) and Essential Proteases.	Arsenic	37-44	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	141-145
32718300-0	2021	In Silico Identification of a Potent Arsenic Based Approved Drug Darinaparsin against SARS-CoV-2: Inhibitor of RNA Dependent RNA polymerase (RdRp) and Essential Proteases.	darinaparsin	65-77	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	141-145
32718300-5	2021	RESULTS: Based on the lower idock score in the catalytic pocket of RdRp, darinaparsin (-82.52 kcal/mol) revealed most effective among them.	darinaparsin	73-85	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	67-71
32720577-0	2021	Plant-derived natural polyphenols as potential antiviral drugs against SARS-CoV-2 via RNA-dependent RNA polymerase (RdRp) inhibition: an in-silico analysis.	Polyphenols	22-33	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	116-120
32720577-5	2021	Interestingly, several plant-derived polyphenols effectively inhibit the RdRp of other RNA viruses.	Polyphenols	37-48	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	73-77
32720577-7	2021	We were curious to study the binding of polyphenols with SARS-CoV-2 RdRp and assess their potential to treat COVID-19.	Polyphenols	40-51	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	68-72
32709886-3	2020	We report here the high-resolution structure of a ternary complex of SARS-CoV-2 nsp16 and nsp10 in the presence of cognate RNA substrate analogue and methyl donor, S-adenosyl methionine (SAM).	S-Adenosylmethionine	187-190	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-95
32709886-4	2020	The nsp16/nsp10 heterodimer is captured in the act of 2"-O methylation of the ribose sugar of the first nucleotide of SARS-CoV-2 mRNA.	ribose sugar	78-90	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	10-15
32709887-4	2020	Here we show the crystal structure of the nsp10-nsp16 complex bound to the pan-MTase inhibitor sinefungin in the active site.	sinefungin	95-105	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	42-47
32691680-5	2021	The compounds cryptophycin 1, cryptophycin 52 and deoxycylindrospermopsin were observed to display encouraging binding energy scores with the PLpro of SARS-CoV-2.	cryptophycin	14-26	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	142-147
32793181-5	2020	Out of 113 quinoline-drugs, elvitegravir and oxolinic acid are able to interact with the NTP entry-channel and thus interfere with the RNA-directed 5"-3" polymerase activity of SARS-CoV-2 RdRp.	quinoline	11-20	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	188-192
32793181-5	2020	Out of 113 quinoline-drugs, elvitegravir and oxolinic acid are able to interact with the NTP entry-channel and thus interfere with the RNA-directed 5"-3" polymerase activity of SARS-CoV-2 RdRp.	elvitegravir	28-40	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	188-192
32793181-5	2020	Out of 113 quinoline-drugs, elvitegravir and oxolinic acid are able to interact with the NTP entry-channel and thus interfere with the RNA-directed 5"-3" polymerase activity of SARS-CoV-2 RdRp.	Oxolinic Acid	45-58	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	188-192
32578982-0	2020	Molecular Basis for ADP-Ribose Binding to the Mac1 Domain of SARS-CoV-2 nsp3.	Adenosine Diphosphate Ribose	20-30	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	72-76
32754651-10	2020	Interestingly, some of the identified drugs (Ornipressin, Lypressin, Examorelin, Polymyxin B1) bind strongly within the binding pockets of both forms of RdRp.	hexarelin	69-79	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	153-157
32691680-5	2021	The compounds cryptophycin 1, cryptophycin 52 and deoxycylindrospermopsin were observed to display encouraging binding energy scores with the PLpro of SARS-CoV-2.	cryptophycin	30-42	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	142-147
32691680-5	2021	The compounds cryptophycin 1, cryptophycin 52 and deoxycylindrospermopsin were observed to display encouraging binding energy scores with the PLpro of SARS-CoV-2.	deoxy-cylindrospermopsin	50-73	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	142-147
32619162-7	2021	p28 interacted with all the three viral proteins and the host ACE-2 receptor by forming several electrostatic and hydrogen bonds with the S-protein, 3CLpro, and PLpro.	Hydrogen	114-122	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	161-166
32686993-5	2021	Among the predicted drugs compounds, clemizole, monorden, spironolactone and tanespimycin showed high binding energies; among the studied repurposing compounds, remdesivir, simeprevir and valinomycin showed high binding energies; among the predicted acidic compounds, acetylursolic acid and hardwickiic acid gave high binding energies; while among the studied anthraquinones and glycosides compounds, ellagitannin and friedelanone showed high binding energies against 3-Chymotrypsin-like protease (3CLpro), Papain-like protease (PLpro), helicase (nsp13), RNA-dependent RNA polymerase (nsp12), 2"-O-ribose methyltransferase (nsp16) of SARS-CoV-2 and DNA-PK and CK2alpha in human.	remdesivir	161-171	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	529-534
32222463-0	2020	Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study.	Ribavirin	0-9	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
32222463-0	2020	Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study.	remdesivir	11-21	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
32222463-0	2020	Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study.	Sofosbuvir	23-33	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
32222463-0	2020	Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study.	galidesivir	35-46	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
32222463-0	2020	Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study.	Tenofovir	52-61	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
32222463-6	2020	KEY FINDINGS: The results suggest the effectiveness of Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir as potent drugs against SARS-CoV-2 since they tightly bind to its RdRp.	Ribavirin	55-64	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	183-187
32222463-6	2020	KEY FINDINGS: The results suggest the effectiveness of Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir as potent drugs against SARS-CoV-2 since they tightly bind to its RdRp.	remdesivir	66-76	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	183-187
32222463-6	2020	KEY FINDINGS: The results suggest the effectiveness of Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir as potent drugs against SARS-CoV-2 since they tightly bind to its RdRp.	Sofosbuvir	78-88	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	183-187
32222463-6	2020	KEY FINDINGS: The results suggest the effectiveness of Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir as potent drugs against SARS-CoV-2 since they tightly bind to its RdRp.	galidesivir	90-101	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	183-187
32222463-6	2020	KEY FINDINGS: The results suggest the effectiveness of Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir as potent drugs against SARS-CoV-2 since they tightly bind to its RdRp.	Tenofovir	107-116	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	183-187
32743211-2	2020	Using a combination of bioinformatics and computational tools, we modelled the 3D structure of the RdRp (RNA-dependent RNA polymerase) of SARS-CoV2 (severe acute respiratory syndrome coronavirus-2) and predicted its probable GTP binding pocket in the active site.	Guanosine Triphosphate	225-228	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-103
32676607-9	2020	We also observe ADP-Mg2+ bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapeutic development.	Adenosine Diphosphate	16-19	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	65-69
32676607-9	2020	We also observe ADP-Mg2+ bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapeutic development.	magnesium ion	20-24	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	65-69
32754599-5	2020	However, remdesivir, an inhibitor of RNA-dependent RNA polymerase (RdRp), has appeared as an auspicious antiviral drug.	remdesivir	9-19	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	67-71
32358203-2	2020	Replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp) enzyme, a target of the antiviral drug remdesivir.	remdesivir	120-130	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	75-79
32597315-4	2021	The binding patterns of these drugs were superior to the previously identified SARS CoV PLpro inhibitor, 6-mercaptopurine (6-MP), suggesting a potential for repurposing these drugs to treat COVID-19.	Mercaptopurine	105-121	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	88-93
32597315-4	2021	The binding patterns of these drugs were superior to the previously identified SARS CoV PLpro inhibitor, 6-mercaptopurine (6-MP), suggesting a potential for repurposing these drugs to treat COVID-19.	Mercaptopurine	123-127	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	88-93
32597315-7	2021	Phenformin, quercetin, and ritonavir all demonstrated prospective binding affinities for COVID-19 PLpro over 50 ns MD simulations, with binding energy values of -56.6, -40.9, and -37.6 kcal/mol, respectively.	Phenformin	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	98-103
32597315-7	2021	Phenformin, quercetin, and ritonavir all demonstrated prospective binding affinities for COVID-19 PLpro over 50 ns MD simulations, with binding energy values of -56.6, -40.9, and -37.6 kcal/mol, respectively.	Quercetin	12-21	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	98-103
32597315-7	2021	Phenformin, quercetin, and ritonavir all demonstrated prospective binding affinities for COVID-19 PLpro over 50 ns MD simulations, with binding energy values of -56.6, -40.9, and -37.6 kcal/mol, respectively.	Ritonavir	27-36	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	98-103
32358203-3	2020	Here we report the cryo-electron microscopy structure of the SARS-CoV-2 RdRp, both in the apo form at 2.8-angstrom resolution and in complex with a 50-base template-primer RNA and remdesivir at 2.5-angstrom resolution.	remdesivir	180-190	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	72-76
32358203-4	2020	The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp, where remdesivir is covalently incorporated into the primer strand at the first replicated base pair, and terminates chain elongation.	remdesivir	132-142	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	120-124
32392072-6	2020	Furthermore, we demonstrate the binding poses of three viral RdRp inhibitors (Galidesivir, Favipiravir, and Penciclovir), which were recently reported to have clinical significance for SARS-CoV-2.	galidesivir	78-89	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	61-65
32475223-3	2021	The present work is an effort for a computational target to block the residual binding protein (RBP) on spike proteins (S), Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins by probiotics namely Plantaricin BN, Plantaricin JLA-9, Plantaricin W, Plantaricin D along with RNA-dependent RNA polymerase (RdRp).	plantaricin	202-213	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	307-311
32475223-3	2021	The present work is an effort for a computational target to block the residual binding protein (RBP) on spike proteins (S), Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins by probiotics namely Plantaricin BN, Plantaricin JLA-9, Plantaricin W, Plantaricin D along with RNA-dependent RNA polymerase (RdRp).	plantaricin	218-229	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	307-311
32475223-3	2021	The present work is an effort for a computational target to block the residual binding protein (RBP) on spike proteins (S), Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins by probiotics namely Plantaricin BN, Plantaricin JLA-9, Plantaricin W, Plantaricin D along with RNA-dependent RNA polymerase (RdRp).	plantaricin	218-229	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	307-311
32475223-3	2021	The present work is an effort for a computational target to block the residual binding protein (RBP) on spike proteins (S), Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins by probiotics namely Plantaricin BN, Plantaricin JLA-9, Plantaricin W, Plantaricin D along with RNA-dependent RNA polymerase (RdRp).	Plantaricin D	252-265	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	307-311
32475223-6	2021	Plantaricin W, D, and JLA-9 were able to block the residues (THR556, ALA558) surrounding the deep grove catalytic site (VAL557) of RdRp making them more therapeutically active for COVID-19.	plantaricin	0-11	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	131-135
32475223-7	2021	Molecular dynamics studies further strengthen stability of the complexes of plantaricin w and SARS-CoV-2 RdRp enzyme, RBD of spike protein, and human ACE2 receptor.	Plantaricin W	76-89	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	105-109
32475223-8	2021	The present study present multi-way options either by blocking RBD on S proteins or interaction of S protein with ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by Plantaricin molecules paving a way that can be useful in the treatment of COVID-19 until some better option will be available.Communicated by Ramaswamy H. Sarma.	plantaricin	193-204	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	151-155
32517353-4	2020	As a computationally predicted, remdesivir-like inhibitor of RNA-dependent RNA polymerase (RdRp)-the central component of the replication/transcription machinery of SARS-CoV-2-silibinin is expected to reduce viral load and impede delayed interferon responses.	remdesivir	32-42	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	91-95
32392072-6	2020	Furthermore, we demonstrate the binding poses of three viral RdRp inhibitors (Galidesivir, Favipiravir, and Penciclovir), which were recently reported to have clinical significance for SARS-CoV-2.	favipiravir	91-102	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	61-65
32392072-6	2020	Furthermore, we demonstrate the binding poses of three viral RdRp inhibitors (Galidesivir, Favipiravir, and Penciclovir), which were recently reported to have clinical significance for SARS-CoV-2.	penciclovir	108-119	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	61-65
32283108-0	2020	Remdesivir and SARS-CoV-2: Structural requirements at both nsp12 RdRp and nsp14 Exonuclease active-sites.	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	65-69
32283108-3	2020	To date, the most promising broad-spectrum class of viral RdRp inhibitors are nucleoside analogues (NAs), with over 25 approved for the treatment of several medically important viral diseases.	Nucleosides	78-88	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	58-62
32283108-8	2020	Additionally, we propose structural and function implications of two previously identified RdRp resistance mutations in relation to resistance against Remdesivir.	remdesivir	151-161	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	91-95
32284326-2	2020	Replication of SARS-CoV-2 depends on the viral RNA-dependent RNA polymerase (RdRp), which is the likely target of the investigational nucleotide analogue remdesivir (RDV).	remdesivir	154-164	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	77-81
32167173-4	2020	We found that theaflavin has a lower idock score in the catalytic pocket of RdRp in SARS-CoV-2 (-9.11 kcal/mol), SARS-CoV (-8.03 kcal/mol), and MERS-CoV (-8.26 kcal/mol) from idock.	theaflavin	14-24	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	76-80
32167173-5	2020	To confirm the result, we discovered that theaflavin has lower binding energy of -8.8 kcal/mol when it docks in the catalytic pocket of SARS-CoV-2 RdRp by using the Blind Docking server.	theaflavin	42-52	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	147-151
32167173-6	2020	Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were found between theaflavin and RdRp.	Hydrogen	101-109	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	150-154
32167173-6	2020	Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were found between theaflavin and RdRp.	theaflavin	135-145	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	150-154
32167173-8	2020	Our results suggest that theaflavin could be a potential SARS-CoV-2 RdRp inhibitor for further study.	theaflavin	25-35	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	68-72
32167180-6	2020	Although overall variation in open-reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively.	nt28144	167-174	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	198-204
32836709-8	2021	Results: Among known inhibitors, remdesivir was found to have the highest affinity for the active site of the RdRp.	remdesivir	33-43	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	110-114
32836709-12	2021	While nucleoside analogs compete with the natural substrate of RdRp, thereby terminating RNA replication, other compounds would physically block entry of the natural substrates into the active site.	Nucleosides	6-16	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	63-67
32511380-6	2020	The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.	Nucleosides	82-92	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	16-20
32284326-2	2020	Replication of SARS-CoV-2 depends on the viral RNA-dependent RNA polymerase (RdRp), which is the likely target of the investigational nucleotide analogue remdesivir (RDV).	remdesivir	166-169	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	77-81
32284326-5	2020	Enzyme kinetics indicated that this RdRp efficiently incorporates the active triphosphate form of RDV (RDV-TP) into RNA.	triphosphoric acid	77-89	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	36-40
32284326-5	2020	Enzyme kinetics indicated that this RdRp efficiently incorporates the active triphosphate form of RDV (RDV-TP) into RNA.	remdesivir	98-101	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	36-40
32284326-5	2020	Enzyme kinetics indicated that this RdRp efficiently incorporates the active triphosphate form of RDV (RDV-TP) into RNA.	remdesivir	103-106	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	36-40
32284326-10	2020	Furthermore, we provide evidence for the target specificity of RDV, as RDV-TP was less efficiently incorporated by the distantly related Lassa virus RdRp, and termination of RNA synthesis was not observed.	remdesivir	63-66	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	149-153
32284326-10	2020	Furthermore, we provide evidence for the target specificity of RDV, as RDV-TP was less efficiently incorporated by the distantly related Lassa virus RdRp, and termination of RNA synthesis was not observed.	remdesivir	71-74	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	149-153
32336957-3	2020	Results: In this study, we applied bioinformatic biodata mining methods to detect CDS and protein sequences of ORF1ab polyprotein of SARS-CoV-2 isolated from oronasopharynx of an Iranian patient.	Cadmium	82-85	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-129
32277040-2	2020	The RNA-dependent RNA polymerase [(RdRp), also named nsp12] is the central component of coronaviral replication and transcription machinery, and it appears to be a primary target for the antiviral drug remdesivir.	remdesivir	202-212	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	35-39
32397643-2	2020	The nsp16 catalytic subunit of the 2"-O-MTase is unusual in its requirement for a stimulatory subunit (nsp10) to catalyze the ribose 2"-O-methylation of the viral RNA cap.	Ribose	126-132	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	103-108
32419838-3	2020	Indeed, the RNA-dependent RNA-polymerases (RdRp) of the two viruses show high sequence and structural homology, supporting the likelihood of binding the Sofosbuvir molecule with similar efficiency.	Sofosbuvir	153-163	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	43-47
32336957-5	2020	The results revealed that the identified ORF1ab polyprotein belongs to a part of nonstructural protein 1 (nsp1) with the high antigenicity residues in a glycine-proline or hydrophobic amino acid rich domain.	Glycine	153-160	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	41-59
32336957-5	2020	The results revealed that the identified ORF1ab polyprotein belongs to a part of nonstructural protein 1 (nsp1) with the high antigenicity residues in a glycine-proline or hydrophobic amino acid rich domain.	Proline	161-168	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	41-59
33821277-3	2021	The structure shows a highly basic and concave surface flanking the active site, comprising several Lys residues of nsp14 and the N-terminal amino group of nsp10.	Lysine	100-103	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	156-161
32511320-3	2020	Here, using polymerase extension experiments, we have demonstrated that the active triphosphate form of Sofosbuvir (a key component of the FDA approved hepatitis C drug EPCLUSA), is incorporated by SARS-CoV-2 RdRp, and blocks further incorporation.	triphosphoric acid	83-95	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	209-213
32511320-3	2020	Here, using polymerase extension experiments, we have demonstrated that the active triphosphate form of Sofosbuvir (a key component of the FDA approved hepatitis C drug EPCLUSA), is incorporated by SARS-CoV-2 RdRp, and blocks further incorporation.	Sofosbuvir	104-114	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	209-213
32511320-4	2020	Using the same molecular insight, we selected the active triphosphate forms of three other anti-viral agents, Alovudine, AZT (an FDA approved HIV/AIDS drug) and Tenofovir alafenamide (TAF, an FDA approved drug for HIV and hepatitis B) for evaluation as inhibitors of SARS-CoV-2 RdRp.	triphosphoric acid	57-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	278-282
32511320-4	2020	Using the same molecular insight, we selected the active triphosphate forms of three other anti-viral agents, Alovudine, AZT (an FDA approved HIV/AIDS drug) and Tenofovir alafenamide (TAF, an FDA approved drug for HIV and hepatitis B) for evaluation as inhibitors of SARS-CoV-2 RdRp.	tenofovir alafenamide	161-182	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	278-282
32511320-5	2020	We demonstrated the ability of these three viral polymerase inhibitors, 3"-fluoro-3"-deoxythymidine triphosphate, 3"-azido-3"-deoxythymidine triphosphate and Tenofovir diphosphate (the active triphosphate forms of Alovudine, AZT and TAF, respectively) to be incorporated by SARS-CoV-2 RdRp, where they also terminate further polymerase extension.	tenofovir diphosphate	158-179	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	285-289
32511320-5	2020	We demonstrated the ability of these three viral polymerase inhibitors, 3"-fluoro-3"-deoxythymidine triphosphate, 3"-azido-3"-deoxythymidine triphosphate and Tenofovir diphosphate (the active triphosphate forms of Alovudine, AZT and TAF, respectively) to be incorporated by SARS-CoV-2 RdRp, where they also terminate further polymerase extension.	triphosphoric acid	100-112	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	285-289
33020707-0	2020	Structural Insight into the Recognition of S-Adenosyl-L-Homocysteine and Sinefungin in SARS-CoV-2 Nsp16/Nsp10 RNA Cap 2"-O-Methyltransferase.	S-Adenosylhomocysteine	43-68	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	104-109
33020707-0	2020	Structural Insight into the Recognition of S-Adenosyl-L-Homocysteine and Sinefungin in SARS-CoV-2 Nsp16/Nsp10 RNA Cap 2"-O-Methyltransferase.	sinefungin	73-83	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	104-109
33020707-4	2020	In the present study, molecular recognition between the two natural nucleoside analogs (S-adenosyl-L-homocysteine (SAH) and sinefungin (SFG)) and the SARS-CoV-2 nsp16/nsp10/m7GpppAC5 was studied using all-atom molecular dynamics simulations and free energy calculations based on MM/GBSA and WaterSwap approaches.	Nucleosides	68-78	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	167-172
33020707-4	2020	In the present study, molecular recognition between the two natural nucleoside analogs (S-adenosyl-L-homocysteine (SAH) and sinefungin (SFG)) and the SARS-CoV-2 nsp16/nsp10/m7GpppAC5 was studied using all-atom molecular dynamics simulations and free energy calculations based on MM/GBSA and WaterSwap approaches.	S-Adenosylhomocysteine	88-113	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	167-172
33020707-4	2020	In the present study, molecular recognition between the two natural nucleoside analogs (S-adenosyl-L-homocysteine (SAH) and sinefungin (SFG)) and the SARS-CoV-2 nsp16/nsp10/m7GpppAC5 was studied using all-atom molecular dynamics simulations and free energy calculations based on MM/GBSA and WaterSwap approaches.	sinefungin	124-134	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	167-172
33020707-4	2020	In the present study, molecular recognition between the two natural nucleoside analogs (S-adenosyl-L-homocysteine (SAH) and sinefungin (SFG)) and the SARS-CoV-2 nsp16/nsp10/m7GpppAC5 was studied using all-atom molecular dynamics simulations and free energy calculations based on MM/GBSA and WaterSwap approaches.	sinefungin	136-139	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	167-172
33102688-5	2020	Our results demonstrate that remdesivir shows the best binding energy on RdRp and saquinvir is the best inhibitor of M pro .	remdesivir	29-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	73-77
33792836-3	2021	In this study, we theorize, using computational simulations, novel mechanisms that may underlie the binding of Rem-P3 to SARS-CoV-2 RdRp-NSPs complex; a multimeric assembly that drives viral RNA replication in human hosts.	rem-p3	111-117	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	132-136
33815808-8	2021	Aloe, azadirachtin, columbin, cirsilineol, nimbiol, nimbocinol and sage exhibited highest binding affinity and interacted with active sites of RdRp surpassing the ability of chloroquine, lamivudine, favipiravir and remdesivir to target the same.	azadirachtin	6-18	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33815808-8	2021	Aloe, azadirachtin, columbin, cirsilineol, nimbiol, nimbocinol and sage exhibited highest binding affinity and interacted with active sites of RdRp surpassing the ability of chloroquine, lamivudine, favipiravir and remdesivir to target the same.	columbin	20-28	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33815808-8	2021	Aloe, azadirachtin, columbin, cirsilineol, nimbiol, nimbocinol and sage exhibited highest binding affinity and interacted with active sites of RdRp surpassing the ability of chloroquine, lamivudine, favipiravir and remdesivir to target the same.	cirsilineol	30-41	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33815808-8	2021	Aloe, azadirachtin, columbin, cirsilineol, nimbiol, nimbocinol and sage exhibited highest binding affinity and interacted with active sites of RdRp surpassing the ability of chloroquine, lamivudine, favipiravir and remdesivir to target the same.	nimbiol	43-50	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33815808-8	2021	Aloe, azadirachtin, columbin, cirsilineol, nimbiol, nimbocinol and sage exhibited highest binding affinity and interacted with active sites of RdRp surpassing the ability of chloroquine, lamivudine, favipiravir and remdesivir to target the same.	NIMBOCINOL	52-62	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33815808-8	2021	Aloe, azadirachtin, columbin, cirsilineol, nimbiol, nimbocinol and sage exhibited highest binding affinity and interacted with active sites of RdRp surpassing the ability of chloroquine, lamivudine, favipiravir and remdesivir to target the same.	Chloroquine	174-185	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33815808-8	2021	Aloe, azadirachtin, columbin, cirsilineol, nimbiol, nimbocinol and sage exhibited highest binding affinity and interacted with active sites of RdRp surpassing the ability of chloroquine, lamivudine, favipiravir and remdesivir to target the same.	Lamivudine	187-197	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33815808-8	2021	Aloe, azadirachtin, columbin, cirsilineol, nimbiol, nimbocinol and sage exhibited highest binding affinity and interacted with active sites of RdRp surpassing the ability of chloroquine, lamivudine, favipiravir and remdesivir to target the same.	favipiravir	199-210	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33815808-8	2021	Aloe, azadirachtin, columbin, cirsilineol, nimbiol, nimbocinol and sage exhibited highest binding affinity and interacted with active sites of RdRp surpassing the ability of chloroquine, lamivudine, favipiravir and remdesivir to target the same.	remdesivir	215-225	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
33815808-13	2021	Non-bonded distance was found to be short enough to form hydrogen bonding or hydrophobic interactions which revealed that these target compounds can strongly bind with RdRp.	Hydrogen	57-65	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	168-172
33825097-8	2022	More surprisingly the top hit, Fonsecin, has naphthalene moiety in its structure, which recruits Tyr268 of SARS-CoV2-PLpro (and Tyr269 of SARS-CoV-PLpro) and has binding energy at par with control (GRL0617).	naphthalene	45-56	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	117-122
33825097-8	2022	More surprisingly the top hit, Fonsecin, has naphthalene moiety in its structure, which recruits Tyr268 of SARS-CoV2-PLpro (and Tyr269 of SARS-CoV-PLpro) and has binding energy at par with control (GRL0617).	naphthalene	45-56	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	147-152
32511290-3	2020	Ongoing clinical trials include Kaletra (a combination of two protease inhibitors approved for HIV treatment), remdesivir (an investigational drug targeting RNA-dependent RNA polymerase [RdRP] of SARS-CoV-2), and hydroxychloroquine (an approved anti-malarial and immuno-modulatory drug).	remdesivir	111-121	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	187-191
33372806-4	2020	From these, 36 phytocompounds with binding affinities higher than the approved reference drugs (remdesivir and sobosivir), were further docked targeting the active sites of SARS-CoV-2, as well as SARS-CoV and HCV RdRp.	sobosivir	111-120	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	213-217
33792836-4	2021	Findings revealed that while ATP-binding stabilized the replicative tripartite, Rem-P3 disintegrated the RdRp-NSP complex, starting with the detachment of the NSP7-NSP8 heterodimer followed by minimal displacement of the second NSP8 subunit (NSP8II).	rem-p3	80-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	105-109
33792836-4	2021	Findings revealed that while ATP-binding stabilized the replicative tripartite, Rem-P3 disintegrated the RdRp-NSP complex, starting with the detachment of the NSP7-NSP8 heterodimer followed by minimal displacement of the second NSP8 subunit (NSP8II).	rem-p3	80-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	159-163
33792836-4	2021	Findings revealed that while ATP-binding stabilized the replicative tripartite, Rem-P3 disintegrated the RdRp-NSP complex, starting with the detachment of the NSP7-NSP8 heterodimer followed by minimal displacement of the second NSP8 subunit (NSP8II).	rem-p3	80-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	164-168
33792836-4	2021	Findings revealed that while ATP-binding stabilized the replicative tripartite, Rem-P3 disintegrated the RdRp-NSP complex, starting with the detachment of the NSP7-NSP8 heterodimer followed by minimal displacement of the second NSP8 subunit (NSP8II).	rem-p3	80-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	228-232
33792836-5	2021	More so, Rem-P3 interacted with a relatively higher affinity (DeltaGbind) while inducing high perturbations across the RdRp-NSP domains.	rem-p3	9-15	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	119-123
33804129-3	2021	In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro).	Methisazone	82-93	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	195-199
33766591-2	2021	SARS-CoV-2 RNA dependent RNA polymerase (RdRp) which is almost preserved across different viral species can be a potential target for development of antiviral drugs, including nucleoside analogues (NA).	Nucleosides	176-186	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	41-45
33766591-6	2021	Afterwards, the clinical development of some NAs including Favipiravir, Sofosbuvir, Ribavirin, Tenofovir, and Remdesivir as potential inhibitors of RdRp, were surveyed.	Ribavirin	84-93	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	148-152
33766591-6	2021	Afterwards, the clinical development of some NAs including Favipiravir, Sofosbuvir, Ribavirin, Tenofovir, and Remdesivir as potential inhibitors of RdRp, were surveyed.	remdesivir	110-120	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	148-152
34904915-0	2022	Cellular miR-150-5p may have a crucial role to play in the biology of SARS-CoV-2 infection by regulating nsp10 gene.	mir-150-5p	9-19	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	105-110
33820739-4	2021	We report the occurrence of a novel mutation at 323aa (314aa of orf1b) of nsp12 (RNA-dependent RNA polymerase) changed to phenylalanine (F) from proline (P), in the first reported isolate of SARS-CoV-2, Wuhan-Hu-1.	Phenylalanine	122-135	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	64-69
33820739-4	2021	We report the occurrence of a novel mutation at 323aa (314aa of orf1b) of nsp12 (RNA-dependent RNA polymerase) changed to phenylalanine (F) from proline (P), in the first reported isolate of SARS-CoV-2, Wuhan-Hu-1.	Proline	145-152	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	64-69
34823857-9	2022	We further measured the inhibitory activity of 5 compounds (rifapentine, velpatasvir, glecaprevir, anidulafungin, and FAD disodium) on SARS-CoV-2 PLpro using Ubiquitin-Rhodamine 110 Gly fluorescent intensity assay.	rifapentine	60-71	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	146-151
34823857-9	2022	We further measured the inhibitory activity of 5 compounds (rifapentine, velpatasvir, glecaprevir, anidulafungin, and FAD disodium) on SARS-CoV-2 PLpro using Ubiquitin-Rhodamine 110 Gly fluorescent intensity assay.	velpatasvir	73-84	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	146-151
34823857-9	2022	We further measured the inhibitory activity of 5 compounds (rifapentine, velpatasvir, glecaprevir, anidulafungin, and FAD disodium) on SARS-CoV-2 PLpro using Ubiquitin-Rhodamine 110 Gly fluorescent intensity assay.	fad disodium	118-130	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	146-151
34823857-9	2022	We further measured the inhibitory activity of 5 compounds (rifapentine, velpatasvir, glecaprevir, anidulafungin, and FAD disodium) on SARS-CoV-2 PLpro using Ubiquitin-Rhodamine 110 Gly fluorescent intensity assay.	ubiquitin-rhodamine	158-177	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	146-151
34823857-9	2022	We further measured the inhibitory activity of 5 compounds (rifapentine, velpatasvir, glecaprevir, anidulafungin, and FAD disodium) on SARS-CoV-2 PLpro using Ubiquitin-Rhodamine 110 Gly fluorescent intensity assay.	Glycine	182-185	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	146-151
34823857-10	2022	The highest inhibition of PLpro activity was seen with rifapentine (IC50: 15.18 muM) and FAD disodium (IC50: 12.39 muM), the drugs with high predicted KIBA scores and binding affinities.	rifapentine	55-66	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	26-31
34823857-10	2022	The highest inhibition of PLpro activity was seen with rifapentine (IC50: 15.18 muM) and FAD disodium (IC50: 12.39 muM), the drugs with high predicted KIBA scores and binding affinities.	fad disodium	89-101	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	26-31
34518755-6	2022	Based on the findings of our study, we report that alpha-hederin, which was found to possess the lowest binding energy (-8.6 kcal/mol) and hence the best binding affinity, is the best inhibitor of RdRp of SARS-CoV-2, among all the compounds screened here.	beta-hederin	51-64	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	197-201
34968879-2	2022	In this study, a detection methodology for SARS-CoV-2 RNA (wildtype and variants of concern) in wastewater was developed based on the detection of different target genes (E and ORF1ab) by polyethylene glycol (PEG) precipitation and digital droplet PCR.	Polyethylene Glycols	188-207	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	177-183
34483364-3	2022	Nicotinamide riboside (NR), which is a naturally occurring analogue of Niacin (vitamin B3), is expected to have therapeutic effects on COVID-19 due to its super close structural similarity to the proven RdRp inhibitors.	nicotinamide-beta-riboside	0-21	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	203-207
34483364-3	2022	Nicotinamide riboside (NR), which is a naturally occurring analogue of Niacin (vitamin B3), is expected to have therapeutic effects on COVID-19 due to its super close structural similarity to the proven RdRp inhibitors.	nicotinamide-beta-riboside	23-25	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	203-207
34483364-6	2022	In the current study, the resulted scores from molecular docking and dynamics simulations as the primary determinative factor as well as the observed reliable binding modes have demonstrated that Nicotinamide Riboside and its active metabolite NMN can target human ACE2 and IMPDH, along with the viral Spro, Mpro, PLpro, and on top of all, RdRp as a potential competitive inhibitor.	nicotinamide-beta-riboside	196-217	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	340-344
34757253-4	2022	Through virtual screening and enzymatic evaluations, nine natural biflavones were confirmed to be effective PLpro inhibitors with IC50 values ranging from 9.5 to 43.2 muM.	biflavones	66-76	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	108-113
34757253-5	2022	Pro-ISG15 cleavage assays further demonstrated that several biflavones exhibited potent inhibitory effects against PLpro-mediated deISGylation, a key process involved in viral immune evasion.	biflavones	60-70	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	115-120
34757253-6	2022	Herein, we report the discovery, antiviral evaluation, structure-activity relationship elucidation and molecular docking investigation of biflavones as potent inhibitors of SARS-CoV-2 PLpro.	biflavones	138-148	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	184-189
34635250-0	2022	A strategy combining 3D-DNA Walker and CRISPR-Cas12a trans-cleavage activity applied to MXene based electrochemiluminescent sensor for SARS-CoV-2 RdRp gene detection.	mxene	88-93	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	146-150
34635250-6	2022	At the same time, we designed an MXene based ECL material: PEI-Ru@Ti3C2@AuNPs, and constructed an ECL biosensor to detect the RdRp gene based on this ECL material as a framework.	mxene	33-38	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-130
34904915-8	2022	A combination of co-transfection and Western blotting experiments also determined the ability of miR-150-5p to inhibit SARS-CoV-2 infection via directly interacting with MRE in the coding strand of nsp10.	mir-150-5p	97-107	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	198-203
34904915-10	2022	Furthermore, this study provides insight into one possible mechanism by which COVID-19-induced changes to miR-150-5p levels may promote SARS-CoV-2 infection via modulating nsp10 expression.	mir-150-5p	106-116	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	172-177
34904832-3	2021	Here, we employed the all-atom molecular dynamics (MD) simulations and binding free energy calculations based on MM-PB(GB)SA and SIE methods to elucidate and compare the binding behaviors of five inhibitors derived from peptidomimetic inhibitors (VIR250 and VIR251) and naphthalene-based inhibitors (GRL-0617, compound 3, and compound Y96) against SARS-CoV-2 PLpro.	naphthalene	270-281	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	359-364
34904832-4	2021	The obtained results revealed that all inhibitors interacting within the PLpro active site are mostly driven by vdW interactions, and the hydrogen bond formation in residues G163 and G271 with peptidomimetics and the Q269 residue with naphthalene-based inhibitors was essential for stabilizing the protein-ligand complexes.	Hydrogen	138-146	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	73-78
34904832-4	2021	The obtained results revealed that all inhibitors interacting within the PLpro active site are mostly driven by vdW interactions, and the hydrogen bond formation in residues G163 and G271 with peptidomimetics and the Q269 residue with naphthalene-based inhibitors was essential for stabilizing the protein-ligand complexes.	naphthalene	235-246	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	73-78
34904832-5	2021	Among the five studied inhibitors, VIR250 exhibited the most binding efficiency with SARS-CoV-2 PLpro, and thus, it was chosen for the rational drug design.	vir250	35-41	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	96-101
34937447-0	2021	Nigellidine (Nigella sativa, black-cumin seed) docking to SARS CoV-2 nsp3 and host inflammatory proteins may inhibit viral replication/transcription and FAS-TNF death signal via TNFR 1/2 blocking.	Nigellidine	0-11	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	69-73
34937447-3	2021	Atomic-Contact-Energy (ACE) and binding-blocking effects were explored of nigellidine (Nigella sativa L.) in the active/catalytic sites of viral-protein nsp3 and host inflammatory/apoptotic signaling-molecules Fas/TNF receptors TNFR1/TNFR2.	Nigellidine	74-85	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	153-157
34937447-7	2021	The nigellidine BE/KI with nsp3 was -7.61 and 2.66, respectively (ACE values were -221.40/-215.62/-113.28).	Nigellidine	4-15	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	27-31
34305173-6	2021	Extensive molecular modeling examination disclosed the potent Taroxaz-104 inhibition of one of the possible active/allosteric sites of nCoV-RdRp, since Taroxaz-104 molecule interacts with at least seven main amino acids of the presumed pocket/cavity of this nCoV-RdRp active site.	taroxaz	62-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	140-144
34981058-1	2021	Boceprevir is an HCV NSP3 inhibitor that has been explored as a repurposed drug for COVID-19.	N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	21-25
34786571-5	2021	The applicability for high-throughput screening of inhibitors is demonstrated with the SARS-CoV-2 nsp3 macrodomain, for which we identify suramin as a moderate-affinity yet non-specific inhibitor.	Suramin	138-145	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	98-102
34961797-3	2021	Molecular dynamics and PELE Monte Carlo simulations highlight favourable binding of hypericin and GRL-0617 to the naphthalene binding pocket of PLpro.	hypericin	84-93	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	144-149
34961797-3	2021	Molecular dynamics and PELE Monte Carlo simulations highlight favourable binding of hypericin and GRL-0617 to the naphthalene binding pocket of PLpro.	naphthalene	114-125	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	144-149
34961797-4	2021	Although not potent as GRL-0617 (45.8 vs 1.6microM for protease activity, respectively), in vitro fluorogenic enzymatic assays with hypericin show concentration-dependent inhibition of both PLpro protease and deubiquitinating activities.	hypericin	132-141	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	190-195
34305173-6	2021	Extensive molecular modeling examination disclosed the potent Taroxaz-104 inhibition of one of the possible active/allosteric sites of nCoV-RdRp, since Taroxaz-104 molecule interacts with at least seven main amino acids of the presumed pocket/cavity of this nCoV-RdRp active site.	taroxaz	62-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	263-267
34305173-6	2021	Extensive molecular modeling examination disclosed the potent Taroxaz-104 inhibition of one of the possible active/allosteric sites of nCoV-RdRp, since Taroxaz-104 molecule interacts with at least seven main amino acids of the presumed pocket/cavity of this nCoV-RdRp active site.	taroxaz	152-159	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	140-144
34305173-6	2021	Extensive molecular modeling examination disclosed the potent Taroxaz-104 inhibition of one of the possible active/allosteric sites of nCoV-RdRp, since Taroxaz-104 molecule interacts with at least seven main amino acids of the presumed pocket/cavity of this nCoV-RdRp active site.	taroxaz	152-159	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	263-267
34633480-0	2021	Partial structure, dampened mobility, and modest impact of a His tag in the SARS-CoV-2 Nsp2 C-terminal region.	Histidine	61-64	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	87-91
34943719-6	2021	Herein, we demonstrated that dexamethasone binds with high affinity to interlukin-1 (IL-1), IL-6, IL-8, IL-12, IL-21, INF2, TGFbeta-1, INF-gamma, CXCL8, some of the receptors, IL-1R, IL-21R, IFNGR, INFAR, IL-6alphaR-gp130, ST2 and the SARS-CoV-2 protein NSP macro X, and 3CLpro, forming stable drug-protein complexes.	Dexamethasone	29-42	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	254-257
34946521-3	2021	Here we applied computational approaches to examine if some polyphenols can also inhibit RNA polymerase (RdRp) in SARS-CoV-2, and we identified some better candidates than remdesivir, the FDA-approved drug against RdRp, in terms of estimated binding affinities.	remdesivir	172-182	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	214-218
34924801-6	2022	On the basis of binding modes and dynamics studies of protein-ligand intercations, ginsenoside Rg2, saikosaponin A, somniferine were found to be the most potent (in silico) inhibitors potentially active against Mpro, PLpro and RdRp, respectively.	ginsenoside Rg2	83-98	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	227-231
34924801-6	2022	On the basis of binding modes and dynamics studies of protein-ligand intercations, ginsenoside Rg2, saikosaponin A, somniferine were found to be the most potent (in silico) inhibitors potentially active against Mpro, PLpro and RdRp, respectively.	saikosaponin D	100-114	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	227-231
34924801-6	2022	On the basis of binding modes and dynamics studies of protein-ligand intercations, ginsenoside Rg2, saikosaponin A, somniferine were found to be the most potent (in silico) inhibitors potentially active against Mpro, PLpro and RdRp, respectively.	Somniferine	116-127	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	227-231
34960205-3	2021	Seven cytotoxic (CTL) and five helper T-cells (HTL) epitopes from ORF1ab were identified using NetCTLpan and NetMHCIIpan algorithms, respectively.	netctlpan	95-104	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	66-72
34960205-3	2021	Seven cytotoxic (CTL) and five helper T-cells (HTL) epitopes from ORF1ab were identified using NetCTLpan and NetMHCIIpan algorithms, respectively.	netmhciipan	109-120	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	66-72
34946521-0	2021	Polyphenols as Potential Inhibitors of SARS-CoV-2 RNA Dependent RNA Polymerase (RdRp).	Polyphenols	0-11	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	80-84
34946521-3	2021	Here we applied computational approaches to examine if some polyphenols can also inhibit RNA polymerase (RdRp) in SARS-CoV-2, and we identified some better candidates than remdesivir, the FDA-approved drug against RdRp, in terms of estimated binding affinities.	Polyphenols	60-71	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	105-109
34873274-4	2021	Molecular docking indicated that favipiravir has similar binding affinities to SARS-CoV-2 and HCoV-NL63 RdRp with LibDock scores of 75 and 74, respectively.	favipiravir	33-44	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	104-108
34873274-5	2021	The LibDock scores of remdesivir to SARS-CoV-2 and HCoV-NL63 were 135 and 151, suggesting that remdesivir may have a higher affinity to HCoV-NL63 compared to SARS-CoV-2 RdRp.	remdesivir	22-32	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	169-173
34881025-5	2021	With a strong affinity toward the viral RNA-dependent RNA polymerase (RdRp), favipiravir could be a promising therapy against SARS-CoV-2, by targeting downstream viral RNA replication.	favipiravir	77-88	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	70-74
34801588-6	2021	In our previous study, we discovered that 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides specifically targets the RdRp of both respiratory syncytial virus (RSV) and influenza A virus.	2-((1h-indol-3-yl)thio)-n-phenyl-acetamides	42-85	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
34801588-7	2021	Thus, we hypothesize that 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides may also have the ability to inhibit SARS-CoV-2 replication by targeting its RdRp activity.	2-((1h-indol-3-yl)thio)-n-phenyl-acetamides	26-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	147-151
34801588-8	2021	In this research, we test a compound library containing 103 of 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides against SARS-CoV-2 RdRp, using our cell-based assay.	2-((1h-indol-3-yl)thio)-n-phenyl-acetamides	63-106	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-130
34543728-8	2021	Structural and energetic comparisons of these inhibitors with Remdesivir and similar nucleotide drugs show that these peptides would be more specific and hence may act as promiscuous antiviral agents against RdRp.	remdesivir	62-72	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	208-212
34633480-7	2021	The 13Cbeta and backbone 13CO, 1HN, 13Calpha, and 15N nuclei of Nsp2"s 45-residue CtR were assigned and used to characterize its structure and dynamics in three contexts; namely: (1) retaining an N-terminal His tag, (2) without the His tag and with an adventitious internal cleavage, and (3) lacking both the His tag and the internal cleavage.	15n	50-53	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	64-68
34633480-7	2021	The 13Cbeta and backbone 13CO, 1HN, 13Calpha, and 15N nuclei of Nsp2"s 45-residue CtR were assigned and used to characterize its structure and dynamics in three contexts; namely: (1) retaining an N-terminal His tag, (2) without the His tag and with an adventitious internal cleavage, and (3) lacking both the His tag and the internal cleavage.	Histidine	309-312	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	64-68
34756886-4	2021	Using a native mass spectrometry-based approach to screen a natural product library for Nsp9 binders, we identified an ent-kaurane natural product, oridonin, capable of binding to purified SARS-CoV-2 Nsp9 with micromolar affinities.	Diterpenes, Kaurane	119-130	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	88-92
34717229-6	2021	Curcumin and diacetylcurcumin showed stability and good binding affinity at the active site of the SARS-CoV-2 RdRp-RNA complex.	Curcumin	0-8	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	110-114
34717229-6	2021	Curcumin and diacetylcurcumin showed stability and good binding affinity at the active site of the SARS-CoV-2 RdRp-RNA complex.	diacetylcurcumin	13-29	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	110-114
34717229-7	2021	Furthermore, to validate the potency of selected compounds, we compared them with Favipiravir and Remdesivir antiviral drugs from our previous analysis on targeting tea bioactive molecules to inhibit RdRp-RNA complex.	remdesivir	98-108	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	200-204
34717229-8	2021	The comparative analysis revealed that the selected compounds showed higher potential to be developed as RdRp-RNA inhibitors than antiviral medicines Remdesivir and Favipiravir.	remdesivir	150-160	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	105-109
34717229-8	2021	The comparative analysis revealed that the selected compounds showed higher potential to be developed as RdRp-RNA inhibitors than antiviral medicines Remdesivir and Favipiravir.	favipiravir	165-176	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	105-109
34756886-4	2021	Using a native mass spectrometry-based approach to screen a natural product library for Nsp9 binders, we identified an ent-kaurane natural product, oridonin, capable of binding to purified SARS-CoV-2 Nsp9 with micromolar affinities.	Diterpenes, Kaurane	119-130	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	200-203
34756886-4	2021	Using a native mass spectrometry-based approach to screen a natural product library for Nsp9 binders, we identified an ent-kaurane natural product, oridonin, capable of binding to purified SARS-CoV-2 Nsp9 with micromolar affinities.	oridonin	148-156	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	88-92
34756886-4	2021	Using a native mass spectrometry-based approach to screen a natural product library for Nsp9 binders, we identified an ent-kaurane natural product, oridonin, capable of binding to purified SARS-CoV-2 Nsp9 with micromolar affinities.	oridonin	148-156	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	200-203
34756886-5	2021	By determining the crystal structure of the Nsp9-oridonin complex, we showed that oridonin binds through a conserved site near Nsp9"s C-terminal GxxxG-helix.	oridonin	49-57	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	44-48
34756886-5	2021	By determining the crystal structure of the Nsp9-oridonin complex, we showed that oridonin binds through a conserved site near Nsp9"s C-terminal GxxxG-helix.	oridonin	49-57	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	127-131
34756886-5	2021	By determining the crystal structure of the Nsp9-oridonin complex, we showed that oridonin binds through a conserved site near Nsp9"s C-terminal GxxxG-helix.	oridonin	82-90	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	44-48
34756886-5	2021	By determining the crystal structure of the Nsp9-oridonin complex, we showed that oridonin binds through a conserved site near Nsp9"s C-terminal GxxxG-helix.	oridonin	82-90	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	127-131
34756886-6	2021	In enzymatic assays oridonin"s binding to Nsp9 reduces its potential to act as substrate for Nsp12"s Nidovirus RdRp-Associated Nucleotidyl transferase (NiRAN) domain.	oridonin	20-28	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	42-46
34756886-8	2021	Accordingly, these preliminary findings suggest the oridonin molecular scaffold may have the potential to be developed into an anti-viral compound to inhibit the function of Nsp9 during coronaviral replication.	oridonin	52-60	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-178
34165771-4	2021	METHODS: A dozen modifications based on remdesivir are tested against SARS-CoV-2 RdRp using combined molecular docking and dynamics simulation in this work.	remdesivir	40-50	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	81-85
34534610-3	2021	We monitored the effect of favipiravir, ribavirin, sofosbuvir triphosphate PSI-7409 and suramin on RdRp binding to RNA immobilized on the chip.	Suramin	88-95	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-103
34534610-4	2021	Suramin precluded interaction of RdRp with RNA and even displaced RdRp from RNA.	Suramin	0-7	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	33-37
34534610-4	2021	Suramin precluded interaction of RdRp with RNA and even displaced RdRp from RNA.	Suramin	0-7	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	66-70
34847746-6	2021	Here, we report six antiviral molecules (F3407-4105, F6523-2250, F6559-0746 from LC and BDG 33693278, BDG 33693315, LAS 34156196 from ASINEX), which show substantial interactions with key amino acid residues of the active site of SARS-CoV-2 RdRP and exhibit higher binding affinity (>7.5 kcalmol-1) than Galidesivir, an Food and Drug Administration-approved inhibitor of the same.	O(6)-n-butyldeoxyguanosine	88-91	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	241-245
34847746-6	2021	Here, we report six antiviral molecules (F3407-4105, F6523-2250, F6559-0746 from LC and BDG 33693278, BDG 33693315, LAS 34156196 from ASINEX), which show substantial interactions with key amino acid residues of the active site of SARS-CoV-2 RdRP and exhibit higher binding affinity (>7.5 kcalmol-1) than Galidesivir, an Food and Drug Administration-approved inhibitor of the same.	O(6)-n-butyldeoxyguanosine	102-105	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	241-245
34847746-6	2021	Here, we report six antiviral molecules (F3407-4105, F6523-2250, F6559-0746 from LC and BDG 33693278, BDG 33693315, LAS 34156196 from ASINEX), which show substantial interactions with key amino acid residues of the active site of SARS-CoV-2 RdRP and exhibit higher binding affinity (>7.5 kcalmol-1) than Galidesivir, an Food and Drug Administration-approved inhibitor of the same.	las 34156196	116-128	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	241-245
34847746-6	2021	Here, we report six antiviral molecules (F3407-4105, F6523-2250, F6559-0746 from LC and BDG 33693278, BDG 33693315, LAS 34156196 from ASINEX), which show substantial interactions with key amino acid residues of the active site of SARS-CoV-2 RdRP and exhibit higher binding affinity (>7.5 kcalmol-1) than Galidesivir, an Food and Drug Administration-approved inhibitor of the same.	galidesivir	304-315	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	241-245
34847746-7	2021	Further, molecular dynamics simulation and Molecular Mechanics Poisson-Boltzmann Surface Area results confirmed that identified molecules with RdRP formed higher stable RdRP-inhibitor(s) complex than RdRP-Galidesvir complex.	galidesvir	205-215	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	200-204
34850656-0	2021	Plant-Derived Natural Non-Nucleoside Analog Inhibitors (NNAIs) against RNA-Dependent RNA Polymerase Complex (nsp7/nsp8/nsp12) of SARS-CoV-2.	Nucleosides	26-36	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	109-113
34850656-0	2021	Plant-Derived Natural Non-Nucleoside Analog Inhibitors (NNAIs) against RNA-Dependent RNA Polymerase Complex (nsp7/nsp8/nsp12) of SARS-CoV-2.	Nucleosides	26-36	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	114-118
34850656-4	2021	Several FDA-approved RdRp "nucleotide analog inhibitors (NAIs)" such as remdesivir, have been repurposed to treat COVID-19 infections.	remdesivir	72-82	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	21-25
34850656-8	2021	NNAIs neither require metabolic activation (unlike NAIs) nor compete with intracellular pool of nucleotide triphosphates (NTPs) for anti-RdRp activity.	nucleotide triphosphates	96-120	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	137-141
34792756-7	2022	Here we present the near-complete backbone and Ile, Leu, and Val methyl group chemical shift assignments of the most C-terminal domain of nsp3, CoV-Y.	Isoleucine	47-50	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	138-142
34619630-2	2021	Molnupiravir is a promising pipeline antiviral drug for treating SARS-CoV-2 infection potentially by targeting RNA-dependent RNA polymerase (RdRp).	EIDD 2801	0-12	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	141-145
34619630-4	2021	Molecular docking revealed that the active form of molnupiravir, beta-D-N4-hydroxycytidine (NHC), has similar binding affinity to RdRp of SARS-CoV-2 and seasonal HCoV-NL63, HCoV-OC43 and HCoV-229E.	EIDD 2801	51-63	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	130-134
34848758-8	2021	Molecular docking studies estimate a good binding propensity of DAPH+Cl- with non-structural proteins (nsp2 and nsp7-nsp-8) and the main protease (Mpro) of SARS-CoV-2.	4,5-dianilinophthalimide	64-68	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	103-107
34848758-9	2021	The molecular dynamics simulation studies attribute the conformationally stable structures of the DAPH+Cl- bound Mpro and nsp2, nsp7-nsp8 complexes as evident from the considerable binding energy values, - 19.2 +- 0.3, - 25.7 +- 0.1, and - 24.5 +- 0.7 kcal/mol, respectively.	4,5-dianilinophthalimide	98-102	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	122-126
34848758-9	2021	The molecular dynamics simulation studies attribute the conformationally stable structures of the DAPH+Cl- bound Mpro and nsp2, nsp7-nsp8 complexes as evident from the considerable binding energy values, - 19.2 +- 0.3, - 25.7 +- 0.1, and - 24.5 +- 0.7 kcal/mol, respectively.	4,5-dianilinophthalimide	98-102	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	128-132
34848758-9	2021	The molecular dynamics simulation studies attribute the conformationally stable structures of the DAPH+Cl- bound Mpro and nsp2, nsp7-nsp8 complexes as evident from the considerable binding energy values, - 19.2 +- 0.3, - 25.7 +- 0.1, and - 24.5 +- 0.7 kcal/mol, respectively.	4,5-dianilinophthalimide	98-102	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	133-137
34512097-5	2021	We investigated the drug-likeness of the plant"s active constituents, such as alkaloids, polyphenols, and flavonoids, as well as their binding affinity for the RdRp enzyme.	Flavonoids	106-116	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	160-164
34920267-4	2022	The mutations in S-glycoprotein trigger the antibody escape/resistance, and mutations in RdRp might cause remdesivir resistance.	remdesivir	106-116	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	89-93
34792756-7	2022	Here we present the near-complete backbone and Ile, Leu, and Val methyl group chemical shift assignments of the most C-terminal domain of nsp3, CoV-Y.	Leucine	52-55	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	138-142
34792756-7	2022	Here we present the near-complete backbone and Ile, Leu, and Val methyl group chemical shift assignments of the most C-terminal domain of nsp3, CoV-Y.	Valine	61-64	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	138-142
34613689-4	2021	Far from merely being cautionary tales about the conduct of scientific research, these errors have had significant practical impact, by hampering a correct understanding of RdRp structure and mechanism, its inhibition by nucleoside analogues such as remdesivir, and the discovery and characterization of such analogues.	Nucleosides	221-231	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	173-177
34613689-4	2021	Far from merely being cautionary tales about the conduct of scientific research, these errors have had significant practical impact, by hampering a correct understanding of RdRp structure and mechanism, its inhibition by nucleoside analogues such as remdesivir, and the discovery and characterization of such analogues.	remdesivir	250-260	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	173-177
34934765-3	2021	In this study, we used pharmacophore fitting and molecular docking to screen and determine docking patterns and the binding affinity of baicalin on 3 major targets of SARS-CoV-2 (3-chymotrypsin-like cysteine protease (3CLpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase).	baicalin	136-144	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	249-254
34934765-4	2021	The obtained data revealed that baicalin has high pharmacophore fitting on 3CLpro and predicted good binding affinity on PLpro.	baicalin	32-40	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	121-126
34829734-3	2021	The present study selected sixty-eight broad-spectrum antiviral marine terpenoids and performed molecular docking against two novel SARS-CoV-2 enzymes (main protease or Mpro or 3CLpro) and RNA-dependent RNA polymerase (RdRp).	Terpenes	71-81	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	219-223
34766880-6	2021	The main protease (Mpro) of SARS-CoV-2 interacted closely with jatamansin (JM), 6,7-dehydroferruginol (FG) and beta-sitosterol (BS), while Papain-like Protease (PLpro) with friedelane-3-one (F3O) and lantadene D (LD) independently.	friedelane-3-one	173-189	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	161-166
34766880-7	2021	Reduced Lantadene A (LAR) exhibited preferable interaction with RNA-dependent-RNA-polymerase (RdRp) whereas Lantadene A (LA) with RdRp and spike-glycoprotein (SG-pro) both target proteins.	rehmannic acid	8-19	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	94-98
34766880-7	2021	Reduced Lantadene A (LAR) exhibited preferable interaction with RNA-dependent-RNA-polymerase (RdRp) whereas Lantadene A (LA) with RdRp and spike-glycoprotein (SG-pro) both target proteins.	rehmannic acid	108-119	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	130-134
34771162-1	2021	This work describes an untargeted analytical approach for the screening, identification, and characterization of the trans-epithelial transport of green tea (Camellia sinensis) catechin extracts with in vitro inhibitory effect against the SARS-CoV-2 papain-like protease (PLpro) activity.	Catechin	177-185	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	272-277
34147744-0	2021	Discovery and optimization of 2-((1H-indol-3-yl)thio)-N-benzyl-acetamides as novel SARS-CoV-2 RdRp inhibitors.	2-((1h-indol-3-yl)thio)-n-benzyl-acetamides	30-73	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	94-98
34147744-2	2021	In this study, several 2-((indol-3-yl)thio)-N-benzyl-acetamides were identified as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors.	2-((indol-3-yl)thio)-n-benzyl-acetamides	23-63	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	124-128
34147744-3	2021	After a two-round optimization, a new series of 2-((indol-3-yl)thio)-N-benzyl-acetamides was designed, synthesized, and evaluated for SARS-CoV-2 RdRp inhibitory effect.	2-((indol-3-yl)thio)-n-benzyl-acetamides	48-88	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	145-149
34730069-7	2021	The molecules were screened based on drug likeliness and the pharmacophore model created in reference to a known potent PLpro inhibitor GRL0617.	GRL0617	136-143	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	120-125
34730069-9	2021	The results showed that Holyrine B, Dihydroarcyriarubin C, Baraphenazine C and 3-hydroxy-3"-N-acetylholyrine A had formed a stable complex in the active site of the PLpro with significant interaction efficiency.	holyrine B	24-34	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	165-170
34730069-9	2021	The results showed that Holyrine B, Dihydroarcyriarubin C, Baraphenazine C and 3-hydroxy-3"-N-acetylholyrine A had formed a stable complex in the active site of the PLpro with significant interaction efficiency.	Dihydroarcyriarubin C	36-57	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	165-170
34730069-9	2021	The results showed that Holyrine B, Dihydroarcyriarubin C, Baraphenazine C and 3-hydroxy-3"-N-acetylholyrine A had formed a stable complex in the active site of the PLpro with significant interaction efficiency.	Baraphenazine C	59-74	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	165-170
34730069-9	2021	The results showed that Holyrine B, Dihydroarcyriarubin C, Baraphenazine C and 3-hydroxy-3"-N-acetylholyrine A had formed a stable complex in the active site of the PLpro with significant interaction efficiency.	CHEMBL4287662	79-110	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	165-170
34427335-6	2021	BAs and RGS-P3 docked in the tunnel-like cavity of RdRp.	boswellic acid	0-3	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	51-55
34746476-11	2021	Echoside A and echoside B showed higher docking score than remdesivir as COVID-19 drug on four target proteins, i.e., spike protein (-7.9 kcal/mol and -7.8 kcal/mol), RBD-ACE2 (-7.5 kcal/mol and -8.2 kcal/mol), 3CLpro (-8.4 kcal/mol and -9.4 kcal/mol) and RdRp (-7.3 kcal/mol and -8.0 kcal/mol).	remdesivir	59-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	211-217
34746476-11	2021	Echoside A and echoside B showed higher docking score than remdesivir as COVID-19 drug on four target proteins, i.e., spike protein (-7.9 kcal/mol and -7.8 kcal/mol), RBD-ACE2 (-7.5 kcal/mol and -8.2 kcal/mol), 3CLpro (-8.4 kcal/mol and -9.4 kcal/mol) and RdRp (-7.3 kcal/mol and -8.0 kcal/mol).	remdesivir	59-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	256-260
34421325-6	2021	Trandolapril, Benazepril, and Moexipril were evaluated as the best non-carcinogenic and non-toxic potential inhibitors of spike glycoprotein, Mpro, and RdRp, respectively.	moexipril	30-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	152-156
34719206-16	2021	Polydatin and resveratrol were found to be specific and selective inhibitors for SARS-CoV-2, 3CLpro and PLpro, viral cysteine proteases.	Resveratrol	14-25	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	104-109
34719206-10	2021	We employed fluorescence resonance energy transfer technology to identify drug"s inhibition in the proteolytic activity of 3CLpro and Plpro.	3clpro	123-129	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	134-139
34719206-12	2021	50% inhibitory concentration (IC50) values of polydatin inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 18.66, 125, 14.6 and 25.42 mum, respectively.	polydatin	46-55	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	86-91
34719206-12	2021	50% inhibitory concentration (IC50) values of polydatin inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 18.66, 125, 14.6 and 25.42 mum, respectively.	polydatin	46-55	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	107-112
34719206-13	2021	IC50 values of resveratrol inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 29.81 ,60.86, 16.35 and19.04 muM, respectively.	Resveratrol	15-26	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	57-62
34719206-13	2021	IC50 values of resveratrol inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 29.81 ,60.86, 16.35 and19.04 muM, respectively.	Resveratrol	15-26	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	78-83
34719206-14	2021	Finally, SPR assay confirmed that polydatin and resveratrol had high affinity to SARS-CoV-2, SARS-CoV 3Clpro, MERS-CoV 3Clpro and PLpro protein.	polydatin	34-43	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	130-135
34719206-14	2021	Finally, SPR assay confirmed that polydatin and resveratrol had high affinity to SARS-CoV-2, SARS-CoV 3Clpro, MERS-CoV 3Clpro and PLpro protein.	Resveratrol	48-59	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	130-135
34719206-16	2021	Polydatin and resveratrol were found to be specific and selective inhibitors for SARS-CoV-2, 3CLpro and PLpro, viral cysteine proteases.	polydatin	0-9	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	104-109
34653416-2	2021	However, the precise working mechanism of RDV when targeting the viral RNA-dependent RNA polymerase (RdRP) has not been fully elucidated.	remdesivir	42-45	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	101-105
34653416-5	2021	A comparative investigation using an enterovirus RdRP further confirms similar delayed intervention and demonstrates that steric hindrance of the RDV-characteristic 1"-cyano at the -4 position is responsible for the "i+3" intervention, although two representative Flaviviridae RdRPs do not exhibit similar behavior.	remdesivir	146-149	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	49-53
34632326-0	2021	6-Thioguanine Blocks SARS-CoV-2 Replication by Inhibition of PLpro.	Thioguanine	0-13	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	61-66
34632326-4	2021	6-TG also inhibited PLpro-catalyzed polyprotein cleavage and de-ISGylation in cells and inhibited proteolytic activity of the purified PLpro domain in vitro.	Thioguanine	0-4	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	20-25
34632326-4	2021	6-TG also inhibited PLpro-catalyzed polyprotein cleavage and de-ISGylation in cells and inhibited proteolytic activity of the purified PLpro domain in vitro.	Thioguanine	0-4	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	135-140
34746186-14	2021	From the overall analyses, we can conclude that Dihydroaltersolanol C, Anthraquinone, Nigbeauvin A, and Catechin are classified as promising candidates for PLpro, thus potentially useful in developing a medicine for COVID-19.	Dihydroaltersolanol C	48-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	156-161
34746186-14	2021	From the overall analyses, we can conclude that Dihydroaltersolanol C, Anthraquinone, Nigbeauvin A, and Catechin are classified as promising candidates for PLpro, thus potentially useful in developing a medicine for COVID-19.	Anthraquinones	71-84	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	156-161
34746186-14	2021	From the overall analyses, we can conclude that Dihydroaltersolanol C, Anthraquinone, Nigbeauvin A, and Catechin are classified as promising candidates for PLpro, thus potentially useful in developing a medicine for COVID-19.	Nigbeauvin A	86-98	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	156-161
34746186-14	2021	From the overall analyses, we can conclude that Dihydroaltersolanol C, Anthraquinone, Nigbeauvin A, and Catechin are classified as promising candidates for PLpro, thus potentially useful in developing a medicine for COVID-19.	Catechin	104-112	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	156-161
34829734-7	2021	Similarly, marine terpenoids such as xiamycin (-9.3), thyrsiferol (-9.2), liouvilloside B (-8.9), liouvilloside A (-8.8), and stachyflin (-8.7) exhibited comparatively higher docking scores than the referral drug remdesivir (-7.4), and favipiravir (-5.7) against the target SARS-CoV-2-RdRp.	remdesivir	213-223	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	285-289
34829734-7	2021	Similarly, marine terpenoids such as xiamycin (-9.3), thyrsiferol (-9.2), liouvilloside B (-8.9), liouvilloside A (-8.8), and stachyflin (-8.7) exhibited comparatively higher docking scores than the referral drug remdesivir (-7.4), and favipiravir (-5.7) against the target SARS-CoV-2-RdRp.	favipiravir	236-247	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	285-289
34829734-7	2021	Similarly, marine terpenoids such as xiamycin (-9.3), thyrsiferol (-9.2), liouvilloside B (-8.9), liouvilloside A (-8.8), and stachyflin (-8.7) exhibited comparatively higher docking scores than the referral drug remdesivir (-7.4), and favipiravir (-5.7) against the target SARS-CoV-2-RdRp.	Terpenes	18-28	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	285-289
34829734-7	2021	Similarly, marine terpenoids such as xiamycin (-9.3), thyrsiferol (-9.2), liouvilloside B (-8.9), liouvilloside A (-8.8), and stachyflin (-8.7) exhibited comparatively higher docking scores than the referral drug remdesivir (-7.4), and favipiravir (-5.7) against the target SARS-CoV-2-RdRp.	xiamycin	37-45	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	285-289
34829734-7	2021	Similarly, marine terpenoids such as xiamycin (-9.3), thyrsiferol (-9.2), liouvilloside B (-8.9), liouvilloside A (-8.8), and stachyflin (-8.7) exhibited comparatively higher docking scores than the referral drug remdesivir (-7.4), and favipiravir (-5.7) against the target SARS-CoV-2-RdRp.	thyrsiferol	54-65	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	285-289
34829734-7	2021	Similarly, marine terpenoids such as xiamycin (-9.3), thyrsiferol (-9.2), liouvilloside B (-8.9), liouvilloside A (-8.8), and stachyflin (-8.7) exhibited comparatively higher docking scores than the referral drug remdesivir (-7.4), and favipiravir (-5.7) against the target SARS-CoV-2-RdRp.	liouvilloside B	74-89	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	285-289
34829734-7	2021	Similarly, marine terpenoids such as xiamycin (-9.3), thyrsiferol (-9.2), liouvilloside B (-8.9), liouvilloside A (-8.8), and stachyflin (-8.7) exhibited comparatively higher docking scores than the referral drug remdesivir (-7.4), and favipiravir (-5.7) against the target SARS-CoV-2-RdRp.	liouvilloside A	98-113	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	285-289
34829734-7	2021	Similarly, marine terpenoids such as xiamycin (-9.3), thyrsiferol (-9.2), liouvilloside B (-8.9), liouvilloside A (-8.8), and stachyflin (-8.7) exhibited comparatively higher docking scores than the referral drug remdesivir (-7.4), and favipiravir (-5.7) against the target SARS-CoV-2-RdRp.	stachyflin	126-136	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	285-289
34681802-6	2021	We identified a novel thioether-amide or guanidine-linker class of potential RdRp inhibitors and calculated favorable binding free energies of representative hits by molecular dynamics simulations coupled with Linear Interaction Energy calculations.	thioether-amide	22-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	77-81
34733263-7	2021	Interestingly, the single-nucleotide variant (SNV) frequency was higher with high percentage of nt14408 mutation in RdRp in severe cases.	nt14408	96-103	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	116-120
34665619-3	2022	PLpro is a promising therapeutic target, albeit challenging owing to featureless P1 and P2 sites recognizing glycine.	Glycine	109-116	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	0-5
34665619-4	2022	To overcome this challenge, we leveraged the cooperativity of multiple shallow binding sites on the PLpro surface, yielding novel 2-phenylthiophenes with nanomolar inhibitory potency.	2-phenylthiophenes	130-148	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	100-105
34681802-6	2021	We identified a novel thioether-amide or guanidine-linker class of potential RdRp inhibitors and calculated favorable binding free energies of representative hits by molecular dynamics simulations coupled with Linear Interaction Energy calculations.	Guanidine	41-50	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	77-81
34684735-3	2021	At first, a structural similarity study against the co-crystallized ligand, S-Adenosyl Methionine (SAM), of SARS-CoV-2 nonstructural protein (nsp10) (PDB ID: 6W4H) was carried out.	S-Adenosylmethionine	76-97	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	142-147
34637693-7	2021	ChEMBL1276156 and PubChem135548348 showed a strong binding affinity with RdRp than its standard inhibitor, Remdesivir.	remdesivir	107-117	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	73-77
34637693-10	2021	The MDS of RdRp-ChEMBL1276156 and RdRp-PubChem135548348 complexes show enhanced stability in comparison to the RdRp-Remdesivir complex.	remdesivir	116-126	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-115
34637693-11	2021	The average interaction energy calculated after 100 ns of MDS was -146.56 and -172.68 KJ mol-1 for RdRp-CHEMBL1276156 complex and RdRp-PubChem135548348 complex, respectively, while -59.90 KJ mol-1 for RdRp-Remdesivir complex.	remdesivir	206-216	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	130-134
34684735-3	2021	At first, a structural similarity study against the co-crystallized ligand, S-Adenosyl Methionine (SAM), of SARS-CoV-2 nonstructural protein (nsp10) (PDB ID: 6W4H) was carried out.	S-Adenosylmethionine	99-102	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	142-147
34637693-11	2021	The average interaction energy calculated after 100 ns of MDS was -146.56 and -172.68 KJ mol-1 for RdRp-CHEMBL1276156 complex and RdRp-PubChem135548348 complex, respectively, while -59.90 KJ mol-1 for RdRp-Remdesivir complex.	remdesivir	206-216	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	201-205
34684735-8	2021	Finally, a density-functional theory (DFT) study suggested vidarabine (182) to be the most relevant SARS-Cov-2 nsp10 inhibitor.	Vidarabine	59-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	111-116
34632942-0	2021	In silico identification of novel benzophenone-coumarin derivatives as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors.	benzophenone	34-46	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	112-116
34632942-0	2021	In silico identification of novel benzophenone-coumarin derivatives as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors.	coumarin	47-55	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	112-116
34632942-1	2021	In this study, we propose our novel benzophenone-coumarin derivatives (BCDs) as potent inhibitors of the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 virus, one of the key targets that are involved in the viral genome replication.	benzophenone	36-48	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	135-139
34632942-1	2021	In this study, we propose our novel benzophenone-coumarin derivatives (BCDs) as potent inhibitors of the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 virus, one of the key targets that are involved in the viral genome replication.	coumarin	49-57	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	135-139
34632942-7	2021	With these findings, we performed molecular dynamics simulations, where BCD-8 edged out remdesivir with its exemplary stable interaction with SARS-CoV-2 RdRp.	remdesivir	88-98	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	153-157
34632942-10	2021	Therefore, we propose BCD-8 as a SARS-CoV-2 RdRp inhibitor, showing higher predicted efficiency than remdesivir in all the in silico experiments conducted.Communicated by Ramaswamy H. Sarma.	bcd-8	22-27	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	44-48
34642689-5	2021	Here we have designed a series of covalent inhibitors by introducing a peptidomimetic linker and reactive electrophilic "warheads" onto analogs of the noncovalent PLpro inhibitor GRL0617.	GRL0617	179-186	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	163-168
34642689-6	2021	We show that the most promising PLpro inhibitor is potent and selective, with activity in cell-based antiviral assays rivaling that of the RNA-dependent RNA polymerase inhibitor remdesivir.	remdesivir	178-188	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	32-37
34517419-2	2021	Remdesivir, the broad-spectrum RdRp inhibitor acts as nucleoside-analogues (NAs).	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	31-35
34639036-0	2021	Tomatidine and Patchouli Alcohol as Inhibitors of SARS-CoV-2 Enzymes (3CLpro, PLpro and NSP15) by Molecular Docking and Molecular Dynamics Simulations.	tomatidine	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	78-83
34909059-6	2021	Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA.	quercetin-3-O-sophoroside	55-80	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	100-104
34517419-2	2021	Remdesivir, the broad-spectrum RdRp inhibitor acts as nucleoside-analogues (NAs).	Nucleosides	54-64	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	31-35
34517419-6	2021	RESULTS: Here, we analyzed the inhibitory effect of theaflavin-3"-O-gallate on SARS CoV-2 RdRp in comparison with remdesivir by molecular-docking study.	Theaflavin-3'-O-gallate	52-75	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-94
34517419-10	2021	CONCLUSIONS: TFMG can block the catalytic residue, NTP entry site, cation binding site, nsp7-nsp12 junction with binding energy of -6.	tfmg	13-17	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	88-92
34326009-5	2021	RESULTS: Docking rilpivirine with main protease (Mpro), papin like protease (PLpro), sprike protein (Spro), human angiotensin converting enzyme-2 (ACE2), and RNA dependent-RNA polymerase (RdRp) yielded binding energies of -8.07, -8.40, -7.55, -9.11, and -8.69 kcal/mol, respectively.	Rilpivirine	17-28	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	188-192
34326009-6	2021	The electrostatic interaction is the key force in stabilizing the RdRp-rilpivirine complex, while van der Waals interaction dominates in the ACE2 rilpivirine case.	Rilpivirine	71-82	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	66-70
34326009-7	2021	Our findings suggest that rilpivirine can inhibit SARS-CoV-2 replication by targeting not only ACE2, but also RdRp and other targets, and therefore, it can be used to invoke altered mechanisms at the pre-entry and post-entry phases.	Rilpivirine	26-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	110-114
34303192-5	2021	Here, we screened non-nucleoside antivirals and found three out of them to be strongest in binding to RdRp out of which two retained binding even using molecular dynamic simulations.	Nucleosides	22-32	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	102-106
34641337-10	2021	Remdesivir, an RdRp inhibitor, exhibited an antiviral EC50 value of 2.4 microM in the same assay.	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	15-19
34533107-9	2021	The results transpired that the binding affinity of Arjunetin is higher than Remdesivir in the RNA binding cavity of RdRp.	arjunetin	52-61	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	117-121
34514487-3	2021	One common group of RdRp inhibitors, 2"-modified nucleotides, are reported to exhibit different behaviors in the SARS-CoV-2 RdRp transcription assay.	2"-modified nucleotides	37-60	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	20-24
34514487-3	2021	One common group of RdRp inhibitors, 2"-modified nucleotides, are reported to exhibit different behaviors in the SARS-CoV-2 RdRp transcription assay.	2"-modified nucleotides	37-60	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	124-128
34514487-11	2021	Our findings are consistent with experimental observations, and more importantly, shed light on the detailed molecular mechanism of SARS-CoV-2 RdRp inhibition by 2"-substituted nucleotide analogs, and may facilitate the rational design of antiviral agents to inhibit SARS-CoV-2 RdRp.	2"-substituted nucleotide	162-187	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
34514487-11	2021	Our findings are consistent with experimental observations, and more importantly, shed light on the detailed molecular mechanism of SARS-CoV-2 RdRp inhibition by 2"-substituted nucleotide analogs, and may facilitate the rational design of antiviral agents to inhibit SARS-CoV-2 RdRp.	2"-substituted nucleotide	162-187	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	278-282
34712904-4	2021	Also, Ct values were determined using SARS-CoV-2-specific oligonucleotides directed to ORF1ab.	Oligonucleotides	58-74	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	87-93
34533107-9	2021	The results transpired that the binding affinity of Arjunetin is higher than Remdesivir in the RNA binding cavity of RdRp.	remdesivir	77-87	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	117-121
34493768-4	2021	According to the fact that C60 fullerene (a sphere-shaped molecule consisting of carbon) has shown inhibitory activity against various protein targets, here the analysis of the potential binding mechanism between SARS-CoV-2 proteins 3CLpro and RdRp with C60 fullerene was done; it has resulted in one and two possible binding mechanisms, respectively.	fullerene C60	27-40	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	244-248
34352100-1	2021	The catalytic subunit of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) contains two active sites that catalyze nucleotidyl-monophosphate transfer (NMPylation).	nucleotidyl-monophosphate	112-137	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	66-70
34352100-4	2021	One study showed that NiRAN transfers NMP to the first residue of RNA-binding protein nsp9; another reported a structure of nsp9 containing two additional N-terminal residues bound to the NiRAN active site but observed NMP transfer to RNA instead.	N-methylpyrrolidone	38-41	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	86-90
34352100-6	2021	Substitutions of the invariant NiRAN residues abolish NMPylation, whereas substitution of a catalytic RdRp Asp residue does not.	Aspartic Acid	107-110	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	102-106
34339634-2	2021	Nucleotide analogs such as remdesivir and favipiravir are thought to interfere with the RNA replication by RdRp.	remdesivir	27-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	107-111
34339634-2	2021	Nucleotide analogs such as remdesivir and favipiravir are thought to interfere with the RNA replication by RdRp.	favipiravir	42-53	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	107-111
34339634-4	2021	However, the process in which these drug candidates and nucleoside triphosphates are taken up by RdRp remains unknown.	nucleoside triphosphates	56-80	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	97-101
34339634-5	2021	In this study, we performed all-atom molecular dynamics simulations to clarify the recognition mechanism of RdRp for these drug candidates and ATP that were at a distance.	Adenosine Triphosphate	143-146	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	108-112
34339634-6	2021	The ligand recognition ability of RdRp decreased in the order of remdesivir, favipiravir, and ATP.	remdesivir	65-75	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	34-38
34339634-6	2021	The ligand recognition ability of RdRp decreased in the order of remdesivir, favipiravir, and ATP.	favipiravir	77-88	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	34-38
34339634-6	2021	The ligand recognition ability of RdRp decreased in the order of remdesivir, favipiravir, and ATP.	Adenosine Triphosphate	94-97	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	34-38
34339634-9	2021	In the common two paths, it was observed that the multiple lysine residues of RdRp carried the ligands to the binding site like a "bucket brigade".	Lysine	59-65	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	78-82
34493768-4	2021	According to the fact that C60 fullerene (a sphere-shaped molecule consisting of carbon) has shown inhibitory activity against various protein targets, here the analysis of the potential binding mechanism between SARS-CoV-2 proteins 3CLpro and RdRp with C60 fullerene was done; it has resulted in one and two possible binding mechanisms, respectively.	Carbon	81-87	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	244-248
34493768-4	2021	According to the fact that C60 fullerene (a sphere-shaped molecule consisting of carbon) has shown inhibitory activity against various protein targets, here the analysis of the potential binding mechanism between SARS-CoV-2 proteins 3CLpro and RdRp with C60 fullerene was done; it has resulted in one and two possible binding mechanisms, respectively.	fullerene C60	254-267	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	244-248
34493768-6	2021	And for RdRp in the first model C60 fullerene blocks RNA synthesis pore and in the second one it prevents binding with Nsp8 co-factor (without this complex formation, RdRp can not perform its initial functions).	Fullerenes	36-45	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	8-12
34493768-6	2021	And for RdRp in the first model C60 fullerene blocks RNA synthesis pore and in the second one it prevents binding with Nsp8 co-factor (without this complex formation, RdRp can not perform its initial functions).	Fullerenes	36-45	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	119-123
34539415-4	2021	Molecular docking analysis revealed strong binding affinities and interactions between the phytocannabinoids and codon mRNAs for ORF1ab, Surface glycoprotein, Envelope protein and Nucleocapsid phosphoprotein from SARS-CoV-2 whole genome which may be due to chemico-biological interactions as a result of nucleophilic/electrophilic attacks between viral nucleotides and cannabinoids.	phytocannabinoids	91-108	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	129-135
34539415-4	2021	Molecular docking analysis revealed strong binding affinities and interactions between the phytocannabinoids and codon mRNAs for ORF1ab, Surface glycoprotein, Envelope protein and Nucleocapsid phosphoprotein from SARS-CoV-2 whole genome which may be due to chemico-biological interactions as a result of nucleophilic/electrophilic attacks between viral nucleotides and cannabinoids.	Cannabinoids	369-381	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	129-135
34247016-3	2021	Herein, I discovered and introduce a new pyrazine derivative, (E)-N-(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (cyanorona-20), as the first potent SARS-CoV-2 RdRp inhibitor with very high selectivity (209- and 45-fold more potent than favipiravir and remdesivir, respectively).	Pyrazines	41-49	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	177-181
34409597-2	2021	Accumulation of mutations in SARS-CoV-2 RdRp may facilitate antigenic drift, generating favipiravir resistance.	favipiravir	88-99	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	40-44
34409597-3	2021	Focusing on the chain-termination mechanism utilized by favipiravir, we used high-throughput interface-based protein design to generate >100,000 designs of the favipiravir-binding site of RdRp and identify mutational hotspots.	favipiravir	56-67	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	188-192
34409597-3	2021	Focusing on the chain-termination mechanism utilized by favipiravir, we used high-throughput interface-based protein design to generate >100,000 designs of the favipiravir-binding site of RdRp and identify mutational hotspots.	favipiravir	160-171	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	188-192
34409597-4	2021	We identified several single-point mutants and designs having a sequence identity of 97-98% with wildtype RdRp, suggesting that SARS-CoV-2 can develop favipiravir resistance with few mutations.	favipiravir	151-162	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	106-110
34247016-3	2021	Herein, I discovered and introduce a new pyrazine derivative, (E)-N-(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (cyanorona-20), as the first potent SARS-CoV-2 RdRp inhibitor with very high selectivity (209- and 45-fold more potent than favipiravir and remdesivir, respectively).	(e)-N-(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide	62-129	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	177-181
34247016-3	2021	Herein, I discovered and introduce a new pyrazine derivative, (E)-N-(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (cyanorona-20), as the first potent SARS-CoV-2 RdRp inhibitor with very high selectivity (209- and 45-fold more potent than favipiravir and remdesivir, respectively).	cyanorona-20	131-143	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	177-181
34247016-3	2021	Herein, I discovered and introduce a new pyrazine derivative, (E)-N-(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (cyanorona-20), as the first potent SARS-CoV-2 RdRp inhibitor with very high selectivity (209- and 45-fold more potent than favipiravir and remdesivir, respectively).	favipiravir	254-265	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	177-181
34476266-6	2021	Molecular docking and binding free energy calculations against RdRp enzyme identified suramin as a potential compound that showed the highest docking score of -7.83 Kcal/mole and binding energy of -80.83 Kcal/mole as a comparison to other compounds.	Suramin	86-93	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	63-67
34331944-2	2021	In the unmodified state, Nsp9 forms an obligate homodimer via an essential GxxxG protein-interaction motif, but its ssRNA-binding mechanism remains unknown.	ssrna	116-121	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	25-29
34119626-8	2021	However, with SDS micelle, it adopted an alpha-helical conformation, suggesting the helical propensity of nsp11.	Sodium Dodecyl Sulfate	14-17	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	106-111
34381216-3	2021	Here, we establish the molecular mechanisms underlying molnupiravir-induced RNA mutagenesis by the viral RNA-dependent RNA polymerase (RdRp).	EIDD 2801	55-67	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	135-139
34381216-4	2021	Biochemical assays show that the RdRp uses the active form of molnupiravir, beta-D-N4-hydroxycytidine (NHC) triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate.	EIDD 2801	62-74	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	33-37
34381216-4	2021	Biochemical assays show that the RdRp uses the active form of molnupiravir, beta-D-N4-hydroxycytidine (NHC) triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate.	beta-d-n4-hydroxycytidine (nhc) triphosphate	76-120	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	33-37
34381216-4	2021	Biochemical assays show that the RdRp uses the active form of molnupiravir, beta-D-N4-hydroxycytidine (NHC) triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate.	Cytidine Triphosphate	148-169	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	33-37
34392751-4	2021	From our results, three complexes containing the ligands with Pubchem IDs: 153012995, 12149203, and 123608715 showed lower binding energies than the control (Ritonavir), indicating that they may become promising inhibitors for PLpro.	Ritonavir	158-167	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	227-232
34578302-5	2021	In light of recently discovered non-canonical RNA caps, we tested various dinucleoside polyphosphate-capped RNAs as substrates for nsp10-nsp16 MTase.	Dinucleoside Phosphates	74-100	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	131-136
34803450-0	2021	beta-Carboline alkaloids induce structural plasticity and inhibition of SARS-CoV-2 nsp3 macrodomain more potently than remdesivir metabolite GS-441524: computational approach.	beta-carboline alkaloids	0-24	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	83-87
34458164-3	2021	Result of molecular docking showed that Isoquercetin potentially binds with the active site/protein binding site of the Spike, RdRP, and Mpro targets with a docking score of -8.22, -6.86, and -9.73 kcal/mole, respectively.	isoquercitrin	40-52	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	127-131
34431452-5	2021	An HIV protease inhibitor, saquinavir showed a good dock score and binding free energy with varied binding interactions against 3CLpro and PLpro.	Saquinavir	27-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	139-144
34431452-6	2021	While, adefovir, a nucleotide HBV DNA polymerase inhibitor exhibited good dock score and binding interactions against RdRp.	adefovir	7-15	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	118-122
34431452-8	2021	The MD simulation runs for 100 ns on 3CLpro-saquinavir, PLpro-saquinavir and RdRp-adefovir complexes using Desmond revealed fairly stable nature of interactions.	3clpro-saquinavir	37-54	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	77-81
34439061-11	2021	Glycyrrhizin and its metabolite 18-beta-glycyrrhetinic acid have shown a strong binding affinity for MPro, helicase, RdRp, spike, and E-channel proteins, while a flavonoid Baicalin also strongly binds against PLpro and RdRp.	Glycyrrhizic Acid	0-12	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	117-121
34439061-11	2021	Glycyrrhizin and its metabolite 18-beta-glycyrrhetinic acid have shown a strong binding affinity for MPro, helicase, RdRp, spike, and E-channel proteins, while a flavonoid Baicalin also strongly binds against PLpro and RdRp.	Glycyrrhizic Acid	0-12	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	209-214
34439061-11	2021	Glycyrrhizin and its metabolite 18-beta-glycyrrhetinic acid have shown a strong binding affinity for MPro, helicase, RdRp, spike, and E-channel proteins, while a flavonoid Baicalin also strongly binds against PLpro and RdRp.	Glycyrrhizic Acid	0-12	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	219-223
34439061-11	2021	Glycyrrhizin and its metabolite 18-beta-glycyrrhetinic acid have shown a strong binding affinity for MPro, helicase, RdRp, spike, and E-channel proteins, while a flavonoid Baicalin also strongly binds against PLpro and RdRp.	18alpha-glycyrrhetinic acid	32-59	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	117-121
34439061-11	2021	Glycyrrhizin and its metabolite 18-beta-glycyrrhetinic acid have shown a strong binding affinity for MPro, helicase, RdRp, spike, and E-channel proteins, while a flavonoid Baicalin also strongly binds against PLpro and RdRp.	18alpha-glycyrrhetinic acid	32-59	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	209-214
34439061-11	2021	Glycyrrhizin and its metabolite 18-beta-glycyrrhetinic acid have shown a strong binding affinity for MPro, helicase, RdRp, spike, and E-channel proteins, while a flavonoid Baicalin also strongly binds against PLpro and RdRp.	18alpha-glycyrrhetinic acid	32-59	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	219-223
34490343-0	2021	Molecular Dynamics Simulations Reveal the Interaction Fingerprint of Remdesivir Triphosphate Pivotal in Allosteric Regulation of SARS-CoV-2 RdRp.	remdesivir	69-79	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	140-144
34490343-3	2021	Remdesivir (RDV) is established to inhibit RNA-dependent RNA polymerase (RdRp) in distinct viral families including Ebola and SARS-CoV-2.	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	73-77
34490343-3	2021	Remdesivir (RDV) is established to inhibit RNA-dependent RNA polymerase (RdRp) in distinct viral families including Ebola and SARS-CoV-2.	remdesivir	12-15	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	73-77
34490343-9	2021	From the interaction fingerprinting it is revealed that the RTP interact with basic and conserved residues that are detrimental for the RdRp activity, therefore it possibly perturbed the catalytic site and blocked the NTP entrance site considerably.	ntp	218-221	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	136-140
34458164-4	2021	Further, MS 3, 7-Hydroxyaloin B, 10-Hydroxyaloin A, showed -9.57, -7.07, -8.57 kcal/mole docking score against Spike, RdRP, and Mpro targets respectively.	3, 7-hydroxyaloin b	12-31	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	118-122
34458164-4	2021	Further, MS 3, 7-Hydroxyaloin B, 10-Hydroxyaloin A, showed -9.57, -7.07, -8.57 kcal/mole docking score against Spike, RdRP, and Mpro targets respectively.	10-Hydroxyaloin A	33-50	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	118-122
34440200-6	2021	We confirmed that SARS-CoV-2 RdRp replicated double-stranded RNA using immunofluorescence staining and the inhibition of RdRp activity by remdesivir and lycorine using this system.	remdesivir	138-148	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	29-33
34443484-6	2021	The synthetic peptides showed PLpro inhibition potencies (IC50s = 1.0-3.5 microM) and binding affinities (Kd = 0.9-7 microM) at the low micromolar range but poor inhibitory activity against Mpro (IC50 > 10 microM).	Peptides	14-22	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	30-35
34440200-6	2021	We confirmed that SARS-CoV-2 RdRp replicated double-stranded RNA using immunofluorescence staining and the inhibition of RdRp activity by remdesivir and lycorine using this system.	remdesivir	138-148	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	121-125
34440200-6	2021	We confirmed that SARS-CoV-2 RdRp replicated double-stranded RNA using immunofluorescence staining and the inhibition of RdRp activity by remdesivir and lycorine using this system.	lycorine	153-161	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	29-33
34440200-6	2021	We confirmed that SARS-CoV-2 RdRp replicated double-stranded RNA using immunofluorescence staining and the inhibition of RdRp activity by remdesivir and lycorine using this system.	lycorine	153-161	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	121-125
34440200-8	2021	Finally, we screened nucleoside and nucleotide analogs and identified adefovir dipivoxil, emtricitabine, telbivudine, entecavir hydrate, moroxydine and rifampin as novel SARS-CoV-2 RdRp inhibitors and therapeutic candidates for COVID-19 This system provides an effective high-throughput screening system platform for developing potential prophylactic and therapeutic drugs for COVID-19 and emerging coronavirus infections.	adefovir dipivoxil	70-88	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	181-185
34222849-1	2021	Background: Tenofovir and emtricitabine interfere with the SARS CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp).	Tenofovir	12-21	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	119-123
34452451-5	2021	Here, we present that these pyridobenzothiazole derivatives also significantly inhibit SARS-CoV-2 RdRp, as demonstrated using both polymerase- and cell-based antiviral assays.	Thiazolo[5,4-f]quinoline	28-47	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	98-102
34370622-7	2021	Additionally, MD simulation supports the robust stability of Ochnaflavone and Licoflavone B against NSP9 at the active sites via hydrophobic interactions, H-bonding, and H-bonding facilitated by water.	ochnaflavone	61-73	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	100-104
34370622-7	2021	Additionally, MD simulation supports the robust stability of Ochnaflavone and Licoflavone B against NSP9 at the active sites via hydrophobic interactions, H-bonding, and H-bonding facilitated by water.	licoflavone B	78-91	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	100-104
34370622-7	2021	Additionally, MD simulation supports the robust stability of Ochnaflavone and Licoflavone B against NSP9 at the active sites via hydrophobic interactions, H-bonding, and H-bonding facilitated by water.	Water	195-200	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	100-104
34181461-6	2021	These same derivatives as well as other hydroxylumisterols and hydroxyvitamin D3 metabolites inhibited RdRP by 50-60%.	hydroxylumisterols	40-58	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	103-107
34181461-6	2021	These same derivatives as well as other hydroxylumisterols and hydroxyvitamin D3 metabolites inhibited RdRP by 50-60%.	hydroxyvitamin d3	63-80	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	103-107
34216889-4	2021	Successive interactions between RdRp (nsp12 alone or in complex with cofactors nsp7-8) and viral RNA demonstrated that the binding affinity values remained the same, but the sites of interaction of RdRp (highly conserved for homologous sequences from different organisms) were altered in the presence of selected antiviral drugs such as Remdesivir, and Sofosbuvir.	remdesivir	337-347	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	32-36
34216889-4	2021	Successive interactions between RdRp (nsp12 alone or in complex with cofactors nsp7-8) and viral RNA demonstrated that the binding affinity values remained the same, but the sites of interaction of RdRp (highly conserved for homologous sequences from different organisms) were altered in the presence of selected antiviral drugs such as Remdesivir, and Sofosbuvir.	remdesivir	337-347	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	79-85
34216889-4	2021	Successive interactions between RdRp (nsp12 alone or in complex with cofactors nsp7-8) and viral RNA demonstrated that the binding affinity values remained the same, but the sites of interaction of RdRp (highly conserved for homologous sequences from different organisms) were altered in the presence of selected antiviral drugs such as Remdesivir, and Sofosbuvir.	remdesivir	337-347	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	198-202
34216889-4	2021	Successive interactions between RdRp (nsp12 alone or in complex with cofactors nsp7-8) and viral RNA demonstrated that the binding affinity values remained the same, but the sites of interaction of RdRp (highly conserved for homologous sequences from different organisms) were altered in the presence of selected antiviral drugs such as Remdesivir, and Sofosbuvir.	Sofosbuvir	353-363	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	32-36
34216889-4	2021	Successive interactions between RdRp (nsp12 alone or in complex with cofactors nsp7-8) and viral RNA demonstrated that the binding affinity values remained the same, but the sites of interaction of RdRp (highly conserved for homologous sequences from different organisms) were altered in the presence of selected antiviral drugs such as Remdesivir, and Sofosbuvir.	Sofosbuvir	353-363	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	79-85
34216889-4	2021	Successive interactions between RdRp (nsp12 alone or in complex with cofactors nsp7-8) and viral RNA demonstrated that the binding affinity values remained the same, but the sites of interaction of RdRp (highly conserved for homologous sequences from different organisms) were altered in the presence of selected antiviral drugs such as Remdesivir, and Sofosbuvir.	Sofosbuvir	353-363	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	198-202
34216889-5	2021	The antiviral drug Sofosbuvir reduced the number of hydrogen bonds formed between RdRp and RNA.	Sofosbuvir	19-29	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	82-86
34216889-5	2021	The antiviral drug Sofosbuvir reduced the number of hydrogen bonds formed between RdRp and RNA.	Hydrogen	52-60	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	82-86
34222849-1	2021	Background: Tenofovir and emtricitabine interfere with the SARS CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp).	Emtricitabine	26-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	119-123
34216889-6	2021	Remdesivir bound more tightly to viral RNA than viral RdRp alone or the nsp12-7-8 hexadecameric complex, resulting in a significant number of hydrogen bonds being formed in the uracil-rich region.	Hydrogen	142-150	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	54-58
34216889-6	2021	Remdesivir bound more tightly to viral RNA than viral RdRp alone or the nsp12-7-8 hexadecameric complex, resulting in a significant number of hydrogen bonds being formed in the uracil-rich region.	Uracil	177-183	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	54-58
34315339-2	2021	This study is aimed to find the most potent ligands from 703 analogs of remdesivir against RNA-dependent RNA polymerase (RdRp) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus .	remdesivir	72-82	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	121-125
34393787-9	2021	Many studies have shown that the presence of a metal ion in the structure can significantly affect the affinity of the compound to key structural elements of the SARS CoV-2, such as Mpro protease, RNA-dependent RNA polymerase (RdRp) and spike protein.	Metals	47-52	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	227-231
34282419-3	2021	Here we show that water-soluble derivatives of alpha-tocopherol have potent antiviral activity and synergize with remdesivir as inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).	Water	18-23	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	187-191
34282419-3	2021	Here we show that water-soluble derivatives of alpha-tocopherol have potent antiviral activity and synergize with remdesivir as inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).	alpha-Tocopherol	47-63	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	187-191
34282419-3	2021	Here we show that water-soluble derivatives of alpha-tocopherol have potent antiviral activity and synergize with remdesivir as inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).	remdesivir	114-124	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	187-191
34282419-5	2021	We subsequently determined that TPGS and other water-soluble derivatives of alpha-tocopherol inhibit the transcriptional activity of purified SARS-CoV-2 RdRp and identified affinity binding sites for these compounds within a conserved, hydrophobic interface between SARS-CoV-2 nonstructural protein 7 and nonstructural protein 8 that is functionally implicated in the assembly of the SARS-CoV-2 RdRp 6 .	Water	47-52	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	153-157
34282419-5	2021	We subsequently determined that TPGS and other water-soluble derivatives of alpha-tocopherol inhibit the transcriptional activity of purified SARS-CoV-2 RdRp and identified affinity binding sites for these compounds within a conserved, hydrophobic interface between SARS-CoV-2 nonstructural protein 7 and nonstructural protein 8 that is functionally implicated in the assembly of the SARS-CoV-2 RdRp 6 .	alpha-Tocopherol	76-92	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	153-157
34282419-6	2021	In summary, we conclude that solubilizing modifications to alpha-tocopherol allow it to interact with the SARS-CoV-2 RdRp, making it an effective antiviral molecule alone and even more so in combination with remdesivir.	alpha-Tocopherol	59-75	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	117-121
34282419-6	2021	In summary, we conclude that solubilizing modifications to alpha-tocopherol allow it to interact with the SARS-CoV-2 RdRp, making it an effective antiviral molecule alone and even more so in combination with remdesivir.	remdesivir	208-218	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	117-121
34441553-6	2021	Among these compounds, retusapurpurin A has shown high affinity to 3CLpro (DeltaG = -9.4 kcal/mol), RdRp (-7.5), RBD (-7.2), NSP13 (-9.4), and ACE2 (-10.4) and potent inhibition of viral entry by forming hydrogen bonds with amino acid residues within viral and human target proteins.	retusapurpurin A	23-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	100-104
34441553-7	2021	In addition, propolis-derived baccharin demonstrated even higher binding affinity towards PLpro (-8.2 kcal/mol).	baccharin	30-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	90-95
34312587-7	2021	From the results, Merimepodib and Dexamethaxone demonstrated the most significant inhibitory potential against the PLpro.	N-3-(3-(3-methoxy-4-oxazol-5-ylphenyl)ureido)benzylcarbamic acid tetrahydrofuran-3-yl ester	18-29	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	115-120
34294141-7	2021	We found Nsp3 interacted with N through its acidic region at N-terminus, while N interacted with Nsp3 through its NTD, which is rich in the basic amino acids.	Amino Acids, Basic	140-157	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	97-101
34312587-7	2021	From the results, Merimepodib and Dexamethaxone demonstrated the most significant inhibitory potential against the PLpro.	dexamethaxone	34-47	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	115-120
34312587-10	2021	whereas Lopinavir (- 7.7 kcal/mol) exhibited the strongest affinity for RdRp.	Lopinavir	8-17	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	72-76
34354677-4	2021	Nucleoside analogs are the most promising RdRp inhibitors and have shown effectiveness in vitro, as well as in clinical settings.	Nucleosides	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	42-46
34232992-0	2021	SARS-CoV-2 Nsp3 unique domain SUD interacts with guanine quadruplexes and G4-ligands inhibit this interaction.	Guanine	49-56	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	11-15
34232992-2	2021	Of note, SARS-CoV Nsp3 contains a SARS-Unique Domain (SUD), which can bind Guanine-rich non-canonical nucleic acid structures called G-quadruplexes (G4) and is essential for SARS-CoV replication.	Guanine	75-82	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	18-22
34232992-3	2021	We show herein that the SARS-CoV-2 Nsp3 protein also contains a SUD domain that interacts with G4s.	Dichlorophen	95-98	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	35-39
34354677-5	2021	One limitation of such RdRp inhibitors is the removal of incorporated nucleoside analogs by SARS-CoV-2 exonuclease (ExoN).	Nucleosides	70-80	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	23-27
34305617-6	2021	In this study, we proposed that remdesivir strongly binds to membrane protein (Mprotein), RNA-dependent RNA polymerase (RDRP), and main protease (Mprotease) of SARS-CoV-2.	remdesivir	32-42	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	120-124
34083449-2	2021	We found that the catalytic subunit of the RdRp, nsp12, ligates two iron-sulfur metal cofactors in sites that were modeled as zinc centers in the available cryo-electron microscopy structures of the RdRp complex.	Iron	68-72	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	43-47
34083449-2	2021	We found that the catalytic subunit of the RdRp, nsp12, ligates two iron-sulfur metal cofactors in sites that were modeled as zinc centers in the available cryo-electron microscopy structures of the RdRp complex.	Iron	68-72	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	199-203
34083449-2	2021	We found that the catalytic subunit of the RdRp, nsp12, ligates two iron-sulfur metal cofactors in sites that were modeled as zinc centers in the available cryo-electron microscopy structures of the RdRp complex.	Sulfur	73-79	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	43-47
34083449-2	2021	We found that the catalytic subunit of the RdRp, nsp12, ligates two iron-sulfur metal cofactors in sites that were modeled as zinc centers in the available cryo-electron microscopy structures of the RdRp complex.	Sulfur	73-79	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	199-203
34083449-2	2021	We found that the catalytic subunit of the RdRp, nsp12, ligates two iron-sulfur metal cofactors in sites that were modeled as zinc centers in the available cryo-electron microscopy structures of the RdRp complex.	Metals	80-85	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	43-47
34083449-2	2021	We found that the catalytic subunit of the RdRp, nsp12, ligates two iron-sulfur metal cofactors in sites that were modeled as zinc centers in the available cryo-electron microscopy structures of the RdRp complex.	Metals	80-85	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	199-203
34083449-4	2021	Oxidation of the clusters by the stable nitroxide TEMPOL caused their disassembly, potently inhibited the RdRp, and blocked SARS-CoV-2 replication in cell culture.	Hydroxylamine	40-49	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	106-110
34083449-4	2021	Oxidation of the clusters by the stable nitroxide TEMPOL caused their disassembly, potently inhibited the RdRp, and blocked SARS-CoV-2 replication in cell culture.	tempol	50-56	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	106-110
34083449-5	2021	These iron-sulfur clusters thus serve as cofactors for the SARS-CoV-2 RdRp and are targets for therapy of COVID-19.	Iron	6-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	70-74
34083449-5	2021	These iron-sulfur clusters thus serve as cofactors for the SARS-CoV-2 RdRp and are targets for therapy of COVID-19.	Sulfur	11-17	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	70-74
34121407-7	2021	Here, the solution-based structural proteomic techniques, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and cross-linking mass spectrometry (XL-MS), illuminate the dynamics of SARS-CoV-2 full-length nsp7 and nsp8 proteins and the nsp7:nsp8 protein complex.	Hydrogen	58-66	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	208-212
34121407-7	2021	Here, the solution-based structural proteomic techniques, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and cross-linking mass spectrometry (XL-MS), illuminate the dynamics of SARS-CoV-2 full-length nsp7 and nsp8 proteins and the nsp7:nsp8 protein complex.	Hydrogen	58-66	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	239-243
34121407-7	2021	Here, the solution-based structural proteomic techniques, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and cross-linking mass spectrometry (XL-MS), illuminate the dynamics of SARS-CoV-2 full-length nsp7 and nsp8 proteins and the nsp7:nsp8 protein complex.	Hydrogen	58-66	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	244-248
34121407-7	2021	Here, the solution-based structural proteomic techniques, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and cross-linking mass spectrometry (XL-MS), illuminate the dynamics of SARS-CoV-2 full-length nsp7 and nsp8 proteins and the nsp7:nsp8 protein complex.	Deuterium	67-76	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	208-212
34121407-7	2021	Here, the solution-based structural proteomic techniques, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and cross-linking mass spectrometry (XL-MS), illuminate the dynamics of SARS-CoV-2 full-length nsp7 and nsp8 proteins and the nsp7:nsp8 protein complex.	Deuterium	67-76	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	239-243
34121407-7	2021	Here, the solution-based structural proteomic techniques, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and cross-linking mass spectrometry (XL-MS), illuminate the dynamics of SARS-CoV-2 full-length nsp7 and nsp8 proteins and the nsp7:nsp8 protein complex.	Deuterium	67-76	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	244-248
34198323-11	2021	We identified three novel compounds (GSK-650394, C646 and BH3I-1) and confirmed suramin and suramin-like compounds as in vitro SARS-CoV-2 RdRp activity inhibitors.	Suramin	80-87	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	138-142
34198323-11	2021	We identified three novel compounds (GSK-650394, C646 and BH3I-1) and confirmed suramin and suramin-like compounds as in vitro SARS-CoV-2 RdRp activity inhibitors.	Suramin	92-99	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	138-142
34198325-7	2021	We developed a protease assay that was used to screen a custom compound library from which we identified dihydrotanshinone I and Ro 08-2750 as compounds that inhibit PLpro in protease and isopeptidase assays and also inhibit viral replication in cell culture-based assays.	dhts	105-124	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	166-171
34198325-7	2021	We developed a protease assay that was used to screen a custom compound library from which we identified dihydrotanshinone I and Ro 08-2750 as compounds that inhibit PLpro in protease and isopeptidase assays and also inhibit viral replication in cell culture-based assays.	2,3,4,10-tetrahydro-7,10-dimethyl-2,4-dioxobenzo(g)pteridine	129-139	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	166-171
34305617-12	2021	Furthermore, the eigenvalues and the trace of the covariance matrix were found to be low in case of Mprotease-remdesivir, Mprotein-remdesivir, and RDRP-remdesivir.	remdesivir	152-162	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	147-151
34305617-13	2021	Binding of remdesivir to Mprotease, Mprotein, and RDRP reduces the average motions in protein due to its strong binding.	remdesivir	11-21	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	50-54
34305617-14	2021	The MMPBSA calculations also suggested that remdesivir has strong binding affinity with Mprotein, Mprotease, and RDRP.	remdesivir	44-54	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	113-117
34305617-8	2021	It has been found that remdesivir binds to Mprotease, Mprotein, and RDRP with -7.8, -7.4, and -7.1 kcal/mol, respectively.	remdesivir	23-33	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	68-72
34305617-9	2021	The structure dynamics study suggested that binding of remdesivir leads to unfolding of RDRP.	remdesivir	55-65	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	88-92
34230209-6	2021	PolyP120 enhanced the proteasomal degradation of both ACE2 and RdRp, thus impairing replication of the British B.1.1.7 SARS-CoV-2 variant.	polyp120	0-8	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	63-67
34154407-1	2021	The catalytic subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) Nsp12 has a unique nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain that transfers nucleoside monophosphates to the Nsp9 protein and the nascent RNA.	nucleoside monophosphates	224-249	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	120-124
34154407-4	2021	Our data show that adenosine and remdesivir triphosphates promote the synthesis of A-less RNAs, as does ppGpp, while amino acid substitutions at the NiRAN-RdRp interface augment activation, suggesting that ligand binding to the NiRAN catalytic site modulates RdRp activity.	remdesivir	33-43	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	259-263
34345611-2	2021	The aim of this study was to predict in silico, using the comparative drug hydroxychloroquine, the working goal of brazilein sappan wood as a candidate for the antiviral drug SARS-CoV-2 against protein S, PLpro, and Mpro.	Hydroxychloroquine	75-93	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	205-210
34345611-7	2021	The above test results indicate that brazilein sappan wood has potential as a SARS-CoV-2 drug candidate, has a stable bond, and that the biological activity of the compound is stronger against S protein than the proteins of PLpro and Mpro.	brazilein sappan	37-53	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	224-229
34154407-1	2021	The catalytic subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) Nsp12 has a unique nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain that transfers nucleoside monophosphates to the Nsp9 protein and the nascent RNA.	nucleoside monophosphates	224-249	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	257-261
34154407-4	2021	Our data show that adenosine and remdesivir triphosphates promote the synthesis of A-less RNAs, as does ppGpp, while amino acid substitutions at the NiRAN-RdRp interface augment activation, suggesting that ligand binding to the NiRAN catalytic site modulates RdRp activity.	Adenosine	19-28	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	155-159
34154407-4	2021	Our data show that adenosine and remdesivir triphosphates promote the synthesis of A-less RNAs, as does ppGpp, while amino acid substitutions at the NiRAN-RdRp interface augment activation, suggesting that ligand binding to the NiRAN catalytic site modulates RdRp activity.	Adenosine	19-28	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	259-263
34154407-4	2021	Our data show that adenosine and remdesivir triphosphates promote the synthesis of A-less RNAs, as does ppGpp, while amino acid substitutions at the NiRAN-RdRp interface augment activation, suggesting that ligand binding to the NiRAN catalytic site modulates RdRp activity.	remdesivir	33-43	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	155-159
34154407-9	2021	Using this assay, we demonstrate that RdRp is allosterically activated by nontemplating phosphorylated nucleotides, including naturally occurring alarmone ppGpp and synthetic remdesivir triphosphate.	alarmone ppgpp	146-160	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	38-42
34131072-2	2021	The SARS-CoV-2 genome encodes the 2"-O-methyltransferase nsp16, which, when bound to the coactivator nsp10, uses S-adenosylmethionine (SAM) as a donor to transfer a methyl group to the first ribonucleotide of the mRNA in the final step of viral mRNA capping.	S-Adenosylmethionine	113-133	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	101-106
34131072-2	2021	The SARS-CoV-2 genome encodes the 2"-O-methyltransferase nsp16, which, when bound to the coactivator nsp10, uses S-adenosylmethionine (SAM) as a donor to transfer a methyl group to the first ribonucleotide of the mRNA in the final step of viral mRNA capping.	S-Adenosylmethionine	135-138	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	101-106
34154407-9	2021	Using this assay, we demonstrate that RdRp is allosterically activated by nontemplating phosphorylated nucleotides, including naturally occurring alarmone ppGpp and synthetic remdesivir triphosphate.	remdesivir	175-185	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	38-42
34131072-4	2021	We determined the X-ray structures of the SARS-CoV-2 2"-O-methyltransferase (the nsp16-nsp10 heterodimer) in complex with its reaction substrates, products, and divalent metal cations.	Metals	170-175	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	87-92
34069681-2	2021	Currently, the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8) has been targeted by numerous inhibitors, e.g., remdesivir, the only provisionally approved treatment to-date, although the clinical impact of these interventions remains inconclusive.	remdesivir	138-148	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	56-60
34182889-6	2021	Six polyphenolic compounds, namely, enterodiol, taxifolin, eriodictyol, leucopelargonidin, morin and myricetin were found to exhibit remarkable binding affinities against the proteases with taxifolin and morin exhibiting the highest binding affinity toward Mpro and PLpro respectively.	polyphenolic compounds	4-26	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	266-271
34182889-6	2021	Six polyphenolic compounds, namely, enterodiol, taxifolin, eriodictyol, leucopelargonidin, morin and myricetin were found to exhibit remarkable binding affinities against the proteases with taxifolin and morin exhibiting the highest binding affinity toward Mpro and PLpro respectively.	2,3-bis(3'-hydroxybenzyl)butane-1,4-diol	36-46	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	266-271
34182889-6	2021	Six polyphenolic compounds, namely, enterodiol, taxifolin, eriodictyol, leucopelargonidin, morin and myricetin were found to exhibit remarkable binding affinities against the proteases with taxifolin and morin exhibiting the highest binding affinity toward Mpro and PLpro respectively.	taxifolin	48-57	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	266-271
34182889-6	2021	Six polyphenolic compounds, namely, enterodiol, taxifolin, eriodictyol, leucopelargonidin, morin and myricetin were found to exhibit remarkable binding affinities against the proteases with taxifolin and morin exhibiting the highest binding affinity toward Mpro and PLpro respectively.	eriodictyol	59-70	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	266-271
34182889-6	2021	Six polyphenolic compounds, namely, enterodiol, taxifolin, eriodictyol, leucopelargonidin, morin and myricetin were found to exhibit remarkable binding affinities against the proteases with taxifolin and morin exhibiting the highest binding affinity toward Mpro and PLpro respectively.	Leucopelargonidin	72-89	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	266-271
34182889-6	2021	Six polyphenolic compounds, namely, enterodiol, taxifolin, eriodictyol, leucopelargonidin, morin and myricetin were found to exhibit remarkable binding affinities against the proteases with taxifolin and morin exhibiting the highest binding affinity toward Mpro and PLpro respectively.	morin	91-96	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	266-271
34182889-6	2021	Six polyphenolic compounds, namely, enterodiol, taxifolin, eriodictyol, leucopelargonidin, morin and myricetin were found to exhibit remarkable binding affinities against the proteases with taxifolin and morin exhibiting the highest binding affinity toward Mpro and PLpro respectively.	myricetin	101-110	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	266-271
34182889-6	2021	Six polyphenolic compounds, namely, enterodiol, taxifolin, eriodictyol, leucopelargonidin, morin and myricetin were found to exhibit remarkable binding affinities against the proteases with taxifolin and morin exhibiting the highest binding affinity toward Mpro and PLpro respectively.	taxifolin	190-199	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	266-271
34205768-0	2021	Targeting 3CLpro and SARS-CoV-2 RdRp by Amphimedon sp.	amphimedon sp	40-53	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	32-36
34290823-0	2021	Reappraisal of trifluperidol against Nsp3 as a potential therapeutic for novel COVID-19: a molecular docking and dynamics study.	Trifluperidol	15-28	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	37-41
34290823-5	2021	The screening and MDS results suggest that trifluperidol could be a novel inhibitor of the ADRP domain of Nsp3.	Trifluperidol	43-56	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	106-110
34136511-5	2021	RdRp is a prime target for Remdesivir and other nucleotides analog-based antiviral drugs.	remdesivir	27-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	0-4
34136511-6	2021	In this study, we showed three bioactive molecules from tea (epicatechin-3,5-di-O-gallate, epigallocatechin-3,5-di-O-gallate, and epigallocatechin-3,4-di-O-gallate) that showed better interaction with critical residues present at the catalytic center and the NTP entry channel of RdRp than antiviral drugs Remdesivir and Favipiravir.	Epicatechin 3,5-di-O-gallate	61-89	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	280-284
34136511-6	2021	In this study, we showed three bioactive molecules from tea (epicatechin-3,5-di-O-gallate, epigallocatechin-3,5-di-O-gallate, and epigallocatechin-3,4-di-O-gallate) that showed better interaction with critical residues present at the catalytic center and the NTP entry channel of RdRp than antiviral drugs Remdesivir and Favipiravir.	epigallocatechin-3,5-di-o-gallate	91-124	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	280-284
34136511-6	2021	In this study, we showed three bioactive molecules from tea (epicatechin-3,5-di-O-gallate, epigallocatechin-3,5-di-O-gallate, and epigallocatechin-3,4-di-O-gallate) that showed better interaction with critical residues present at the catalytic center and the NTP entry channel of RdRp than antiviral drugs Remdesivir and Favipiravir.	epigallocatechin-3,4-di-o-gallate	130-163	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	280-284
34136511-6	2021	In this study, we showed three bioactive molecules from tea (epicatechin-3,5-di-O-gallate, epigallocatechin-3,5-di-O-gallate, and epigallocatechin-3,4-di-O-gallate) that showed better interaction with critical residues present at the catalytic center and the NTP entry channel of RdRp than antiviral drugs Remdesivir and Favipiravir.	ntp	259-262	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	280-284
34136511-6	2021	In this study, we showed three bioactive molecules from tea (epicatechin-3,5-di-O-gallate, epigallocatechin-3,5-di-O-gallate, and epigallocatechin-3,4-di-O-gallate) that showed better interaction with critical residues present at the catalytic center and the NTP entry channel of RdRp than antiviral drugs Remdesivir and Favipiravir.	remdesivir	306-316	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	280-284
34136511-6	2021	In this study, we showed three bioactive molecules from tea (epicatechin-3,5-di-O-gallate, epigallocatechin-3,5-di-O-gallate, and epigallocatechin-3,4-di-O-gallate) that showed better interaction with critical residues present at the catalytic center and the NTP entry channel of RdRp than antiviral drugs Remdesivir and Favipiravir.	favipiravir	321-332	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	280-284
34248355-6	2021	Based on comparative molecular docking and simulation studies of the selected phytocompounds with SARS-CoV-2 RdRp revealed that EBDGp possesses a stronger binding affinity (-23.32 kcal/mol) and stability than other phytocompounds and reference compound, Remdesivir (-19.36 kcal/mol).	remdesivir	254-264	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	109-113
34248355-8	2021	Molecular docking and dynamic simulation results confirmed that EBDGp has better inhibitory potential than Remdesivir and can be an effective novel drug for SARS-CoV-2 RdRp.	remdesivir	107-117	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	168-172
34206274-1	2021	SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) protein is the target for the antiviral drug Remdesivir (RDV).	remdesivir	92-102	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	41-45
34206274-1	2021	SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) protein is the target for the antiviral drug Remdesivir (RDV).	remdesivir	104-107	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	41-45
34206274-4	2021	The current study sought to investigate whether A97V and P323L mutations influence the binding of RDV to the RdRp of SARS-CoV-2 compared to wild-type (WT).	remdesivir	98-101	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	109-113
34206274-5	2021	The interaction of RDV with WT-, A97V-, and P323L-RdRp were measured using molecular dynamic (MD) simulations, and the free binding energies were extracted.	remdesivir	19-22	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	50-54
34206274-6	2021	Results showed that RDV that bound to WT- and A97V-RdRp had a similar dynamic motion and internal residue fluctuations, whereas RDV interaction with P323L-RdRp exhibited a tighter molecular conformation, with a high internal motion near the active site.	remdesivir	20-23	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	51-55
34206274-6	2021	Results showed that RDV that bound to WT- and A97V-RdRp had a similar dynamic motion and internal residue fluctuations, whereas RDV interaction with P323L-RdRp exhibited a tighter molecular conformation, with a high internal motion near the active site.	remdesivir	20-23	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	155-159
34206274-6	2021	Results showed that RDV that bound to WT- and A97V-RdRp had a similar dynamic motion and internal residue fluctuations, whereas RDV interaction with P323L-RdRp exhibited a tighter molecular conformation, with a high internal motion near the active site.	remdesivir	128-131	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	155-159
34206274-7	2021	This was further corroborated with RDV showing a higher binding affinity to P323L-RdRp (-24.1 kcal/mol) in comparison to WT-RdRp (-17.3 kcal/mol).	remdesivir	35-38	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	82-86
34206274-8	2021	This study provides insight into the potential significance of administering RDV to patients carrying the SARS-CoV-2 P323L-RdRp mutation, which may have a more favourable chance of alleviating the SARS-CoV-2 illness in comparison to WT-RdRp carriers, thereby suggesting further scientific consensus for the usage of Remdesivir as clinical candidate against COVID-19.	remdesivir	77-80	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	123-127
34206274-8	2021	This study provides insight into the potential significance of administering RDV to patients carrying the SARS-CoV-2 P323L-RdRp mutation, which may have a more favourable chance of alleviating the SARS-CoV-2 illness in comparison to WT-RdRp carriers, thereby suggesting further scientific consensus for the usage of Remdesivir as clinical candidate against COVID-19.	remdesivir	316-326	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	123-127
34206274-8	2021	This study provides insight into the potential significance of administering RDV to patients carrying the SARS-CoV-2 P323L-RdRp mutation, which may have a more favourable chance of alleviating the SARS-CoV-2 illness in comparison to WT-RdRp carriers, thereby suggesting further scientific consensus for the usage of Remdesivir as clinical candidate against COVID-19.	remdesivir	316-326	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	236-240
34151745-5	2021	Among these compounds, mycalamide A was identified as a potent inhibitor of SARS-CoV-2 RdRp that showed the best and stable interaction during molecular dynamic simulation, with residues (Asp760 and Asp761) found in the catalytic domain of RdRp.	mycalamide A	23-35	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	87-91
34151745-5	2021	Among these compounds, mycalamide A was identified as a potent inhibitor of SARS-CoV-2 RdRp that showed the best and stable interaction during molecular dynamic simulation, with residues (Asp760 and Asp761) found in the catalytic domain of RdRp.	mycalamide A	23-35	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	240-244
34311539-13	2021	Raltegravir, an anti-HIV drug, was observed to be the best compound against RdRp based on docking binding energy (-9.5 kcal/mole) and MD results.	Raltegravir Potassium	0-11	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	76-80
34069681-2	2021	Currently, the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8) has been targeted by numerous inhibitors, e.g., remdesivir, the only provisionally approved treatment to-date, although the clinical impact of these interventions remains inconclusive.	remdesivir	138-148	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	79-83
34069681-2	2021	Currently, the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8) has been targeted by numerous inhibitors, e.g., remdesivir, the only provisionally approved treatment to-date, although the clinical impact of these interventions remains inconclusive.	remdesivir	138-148	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	84-88
34069681-4	2021	Here, we propose a framework to monitor the emergence of antiviral resistance, and as a proof of concept, we address the interaction between RdRp and remdesivir.	remdesivir	150-160	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	141-145
34817369-4	2021	In this study, the virtual screening followed by an in-depth docking study of the Compounds Library found that natural compound Cyclocurcumin and Silybin B have strong interaction with RdRp and much better than the remdesivir with free binding energy and inhibition constant value as ezOE-6.29 kcal/mol and 58.39 microMezOE, and ezOE-7.93kcal/mol and 45.3 microMezOE, respectively.	Cyclocurcumin	128-141	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	185-189
34159141-8	2021	Justicidin D had binding affinities of -8.7, -8.1, and -7.6 kcal mol-1 on RdRp, 3CLpro, and spike, respectively.	justicidins	0-12	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	74-78
34159141-9	2021	10-methoxycamptothecin had binding affinities of -8.5 and -8.2 kcal mol-1 on RdRp and spike, respectively.	10-methoxycamptothecin	0-22	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	77-81
34159141-10	2021	Inoxanthone had binding affinities of -8.3 and -8.1 kcal mol-1 on RdRp and spike, respectively, while binding affinities of caribine were -9.0 and -7.5 mol-1 on 3CLpro and spike, respectively.	blancoxanthone	0-11	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	66-70
34393433-2	2021	Hence, we report the binding features of rutin, Luteolin, Salvianolic acid A, Rosmarinic acid and p-Coumaric acid with the target protein SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) for further consideration.	Rutin	41-46	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	186-190
34393433-2	2021	Hence, we report the binding features of rutin, Luteolin, Salvianolic acid A, Rosmarinic acid and p-Coumaric acid with the target protein SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) for further consideration.	rosmarinic acid	78-93	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	186-190
33594371-7	2021	A series of novel 2-phenylthiophene-based non-covalent SARS-CoV-2 PLpro inhibitors were obtained, culminating in low nanomolar potency.	2-Phenylthiophene	18-35	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	66-71
34817369-4	2021	In this study, the virtual screening followed by an in-depth docking study of the Compounds Library found that natural compound Cyclocurcumin and Silybin B have strong interaction with RdRp and much better than the remdesivir with free binding energy and inhibition constant value as ezOE-6.29 kcal/mol and 58.39 microMezOE, and ezOE-7.93kcal/mol and 45.3 microMezOE, respectively.	Silybin	146-155	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	185-189
34393433-2	2021	Hence, we report the binding features of rutin, Luteolin, Salvianolic acid A, Rosmarinic acid and p-Coumaric acid with the target protein SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) for further consideration.	p-coumaric acid	98-113	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	186-190
34817369-4	2021	In this study, the virtual screening followed by an in-depth docking study of the Compounds Library found that natural compound Cyclocurcumin and Silybin B have strong interaction with RdRp and much better than the remdesivir with free binding energy and inhibition constant value as ezOE-6.29 kcal/mol and 58.39 microMezOE, and ezOE-7.93kcal/mol and 45.3 microMezOE, respectively.	ezoe	284-288	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	185-189
34817369-4	2021	In this study, the virtual screening followed by an in-depth docking study of the Compounds Library found that natural compound Cyclocurcumin and Silybin B have strong interaction with RdRp and much better than the remdesivir with free binding energy and inhibition constant value as ezOE-6.29 kcal/mol and 58.39 microMezOE, and ezOE-7.93kcal/mol and 45.3 microMezOE, respectively.	ezoe	329-333	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	185-189
34870149-4	2021	Molecular docking with canthin-6-one 9-O-beta-glucopyranoside showed highest binding affinity and less binding energy with both PLpro and Mpro/3CLpro proteases and was subjected to molecular dynamic (MD) simulations for a period of 100ns.	canthin-6-one	23-36	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	128-133
34161118-8	2021	It was found that the Carvedilol molecule was the best against RNA dependent RNA polymerase (RdRp) protein of SARS-CoV-2 (Tab.	Carvedilol	22-32	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	93-97
34189273-3	2021	We identified lysine-143 in the equine arteritis virus (EAV) protein, nsp7, as a primary site of in vitro GMP attachment via a phosphoramide bond.	Lysine	14-20	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	70-74
34189273-3	2021	We identified lysine-143 in the equine arteritis virus (EAV) protein, nsp7, as a primary site of in vitro GMP attachment via a phosphoramide bond.	Guanosine Monophosphate	106-109	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	70-74
34189273-3	2021	We identified lysine-143 in the equine arteritis virus (EAV) protein, nsp7, as a primary site of in vitro GMP attachment via a phosphoramide bond.	phosphoramide	127-140	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	70-74
34189273-4	2021	In SARS-CoV-2 replicase proteins, we demonstrate nsp12-mediated nucleotidylation of nsp7 lysine-2.	Lysine	89-95	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	84-88
34870153-7	2021	Interestingly, the computational docking analysis of the best inhibitory binding mode of teriflunomide in the binding pocket of the active site of the SARS-CoV-2 RdRp revealed that teriflunomide may exhibit significantly stronger inhibitory binding interactions and better inhibitory binding affinities (teriflunomide has considerably lower binding energies of -9.70 and -7.80 kcal/mol with RdRp-RNA and RdRp alone, respectively) than both references.	teriflunomide	89-102	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	162-166
34870153-7	2021	Interestingly, the computational docking analysis of the best inhibitory binding mode of teriflunomide in the binding pocket of the active site of the SARS-CoV-2 RdRp revealed that teriflunomide may exhibit significantly stronger inhibitory binding interactions and better inhibitory binding affinities (teriflunomide has considerably lower binding energies of -9.70 and -7.80 kcal/mol with RdRp-RNA and RdRp alone, respectively) than both references.	teriflunomide	89-102	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	391-395
34870153-7	2021	Interestingly, the computational docking analysis of the best inhibitory binding mode of teriflunomide in the binding pocket of the active site of the SARS-CoV-2 RdRp revealed that teriflunomide may exhibit significantly stronger inhibitory binding interactions and better inhibitory binding affinities (teriflunomide has considerably lower binding energies of -9.70 and -7.80 kcal/mol with RdRp-RNA and RdRp alone, respectively) than both references.	teriflunomide	89-102	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	404-408
34870153-7	2021	Interestingly, the computational docking analysis of the best inhibitory binding mode of teriflunomide in the binding pocket of the active site of the SARS-CoV-2 RdRp revealed that teriflunomide may exhibit significantly stronger inhibitory binding interactions and better inhibitory binding affinities (teriflunomide has considerably lower binding energies of -9.70 and -7.80 kcal/mol with RdRp-RNA and RdRp alone, respectively) than both references.	teriflunomide	181-194	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	162-166
34870153-7	2021	Interestingly, the computational docking analysis of the best inhibitory binding mode of teriflunomide in the binding pocket of the active site of the SARS-CoV-2 RdRp revealed that teriflunomide may exhibit significantly stronger inhibitory binding interactions and better inhibitory binding affinities (teriflunomide has considerably lower binding energies of -9.70 and -7.80 kcal/mol with RdRp-RNA and RdRp alone, respectively) than both references.	teriflunomide	181-194	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	391-395
34870153-7	2021	Interestingly, the computational docking analysis of the best inhibitory binding mode of teriflunomide in the binding pocket of the active site of the SARS-CoV-2 RdRp revealed that teriflunomide may exhibit significantly stronger inhibitory binding interactions and better inhibitory binding affinities (teriflunomide has considerably lower binding energies of -9.70 and -7.80 kcal/mol with RdRp-RNA and RdRp alone, respectively) than both references.	teriflunomide	181-194	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	404-408
34870153-7	2021	Interestingly, the computational docking analysis of the best inhibitory binding mode of teriflunomide in the binding pocket of the active site of the SARS-CoV-2 RdRp revealed that teriflunomide may exhibit significantly stronger inhibitory binding interactions and better inhibitory binding affinities (teriflunomide has considerably lower binding energies of -9.70 and -7.80 kcal/mol with RdRp-RNA and RdRp alone, respectively) than both references.	teriflunomide	304-317	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	162-166
34870153-7	2021	Interestingly, the computational docking analysis of the best inhibitory binding mode of teriflunomide in the binding pocket of the active site of the SARS-CoV-2 RdRp revealed that teriflunomide may exhibit significantly stronger inhibitory binding interactions and better inhibitory binding affinities (teriflunomide has considerably lower binding energies of -9.70 and -7.80 kcal/mol with RdRp-RNA and RdRp alone, respectively) than both references.	teriflunomide	304-317	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	391-395
34870153-7	2021	Interestingly, the computational docking analysis of the best inhibitory binding mode of teriflunomide in the binding pocket of the active site of the SARS-CoV-2 RdRp revealed that teriflunomide may exhibit significantly stronger inhibitory binding interactions and better inhibitory binding affinities (teriflunomide has considerably lower binding energies of -9.70 and -7.80 kcal/mol with RdRp-RNA and RdRp alone, respectively) than both references.	teriflunomide	304-317	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	404-408
34870153-9	2021	In conclusion, the current research paved the way to practically prove the hypothetical theory of the promising abilities of teriflunomide to successfully attack the SARS-CoV-2 particles and inhibit their replication in a triple mode of action through integrating the newly-discovered nCoV-RdRp-inhibiting properties with the previously-known two anticoronaviral mechanisms of action.	teriflunomide	125-138	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	290-294
34131556-9	2021	Furthermore, representative docking complexes were validated using molecular dynamics simulations and mechanistic studies at 100 ns was carried on nucleocapsid and nsp10 proteins with curcumin complexes which resulted in stable and efficient binding energies and correlated with that of docked binding energies of the complexes.	Curcumin	184-192	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	164-169
35597097-1	2022	A series of amino acid based 7H-pyrrolo(2,3-d)pyrimidines were designed and synthesized to discern the structure activity relationships against the SARS-CoV-2 nsp3 macrodomain (Mac1), an ADP-ribosylhydrolase that is critical for coronavirus replication and pathogenesis.	7h-pyrrolo(2,3-d)pyrimidines	29-57	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	159-163
35345533-8	2022	The structure-activity relationships established through molecular docking studies showed that 3-Cl BHB structure strongly binds to the receptors Mpro (-8.90 Kcal/mol) and RdRp (-8.60 Kcal/mol) which confirm its inhibition activity against COVID-19.	3-cl bhb	95-103	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	172-176
35609344-6	2022	Pyronaridine inhibited the viral PLpro activity in vitro (IC50 of 1.8 muM) without any effect on Mpro, indicating a possible molecular mechanism involved in its ability to inhibit SARS-CoV-2 replication.	pyronaridine	0-12	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	33-38
35578710-3	2022	In this study, a voltammetric genosensor was developed for the determination of SARS-CoV-2 RdRP gene based on the format of cDNA probe/Au@CD core-shell NPs/graphite nanocrystals (GNCs)/paper electrode.	Graphite	156-164	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	91-95
35578710-5	2022	This genosensor was exposed to different concentrations of virus gene and then the hybridization between cDNA probe and RdRP gene was monitored by redox-active toluidine blue (TB).	Tolonium Chloride	160-174	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	120-124
35578710-5	2022	This genosensor was exposed to different concentrations of virus gene and then the hybridization between cDNA probe and RdRP gene was monitored by redox-active toluidine blue (TB).	Tolonium Chloride	176-178	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	120-124
35578710-6	2022	With increasing the RdRP concentration, the reduction peak current of TB enhanced in a linear range of 0.50 pM-12.00 nM according to the regression equation of I (muA) = 7.60 log CRdRP (pM) + 25.78.	Tolonium Chloride	70-72	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	20-24
35475235-0	2022	Unraveling the binding mechanism of the active form of Remdesivir to RdRp of SARS-CoV-2 and designing new potential analogues: Insights from molecular dynamics simulations.	remdesivir	55-65	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	69-73
35475235-1	2022	The binding of the active form of Remdesivir (RTP) to RNA-dependent RNA Polymerase (RdRp) of SARS-CoV-2 was studied using molecular dynamics simulation.	remdesivir	34-44	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	84-88
35510477-3	2022	The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before.	Sofosbuvir	52-62	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	177-181
35510477-3	2022	The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before.	Sofosbuvir	52-62	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	208-212
35510477-3	2022	The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before.	galidesivir	64-75	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	177-181
35510477-3	2022	The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before.	galidesivir	64-75	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	208-212
35510477-3	2022	The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before.	Ribavirin	77-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	177-181
35510477-3	2022	The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before.	Ribavirin	77-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	208-212
35510477-3	2022	The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before.	remdesivir	91-101	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	177-181
35510477-3	2022	The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before.	remdesivir	91-101	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	208-212
35510477-3	2022	The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before.	nucleotide triphosphates	134-158	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	177-181
35510477-4	2022	Additionally, other compounds such as setrobuvir, YAK, IDX-184 and modified GTP compounds 2, 3 and 4 show potential calculated average binding affinities against R. oryzae RdRp.	setrobuvir	38-48	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	172-176
35510477-4	2022	Additionally, other compounds such as setrobuvir, YAK, IDX-184 and modified GTP compounds 2, 3 and 4 show potential calculated average binding affinities against R. oryzae RdRp.	Guanosine Triphosphate	76-79	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	172-176
35582905-0	2022	Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1.	omicron ba	40-50	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	8-14
34997207-5	2022	Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1alpha,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis.	Calcitriol	96-125	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	10-14
34997207-5	2022	Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1alpha,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis.	Metformin	127-136	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	10-14
34997207-5	2022	Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1alpha,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis.	Metformin	127-136	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	160-164
34997207-5	2022	Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1alpha,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis.	polydatin	140-149	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	10-14
34997207-5	2022	Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1alpha,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis.	polydatin	140-149	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	160-164
35259661-5	2022	The present study focused on curcumin derivatives with reliable ADME profile and high molecular binding potency to different SARS-CoV-2 target enzymes (3CLPro, PLpro, NSP7/8/12, NSP7/8/12 +RNA, NSP15, NSP16, Spike, Spike+ACE).	Curcumin	29-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	160-165
35259661-5	2022	The present study focused on curcumin derivatives with reliable ADME profile and high molecular binding potency to different SARS-CoV-2 target enzymes (3CLPro, PLpro, NSP7/8/12, NSP7/8/12 +RNA, NSP15, NSP16, Spike, Spike+ACE).	Curcumin	29-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	167-176
35390745-9	2022	Our results suggested that isoskimmiwallin and terflavin A are potential inhibitors of RdRp, whereas isoquercitrin and isoorientin are the lead molecules against Mpro.	isoskimmiwallin	27-42	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	87-91
35259661-5	2022	The present study focused on curcumin derivatives with reliable ADME profile and high molecular binding potency to different SARS-CoV-2 target enzymes (3CLPro, PLpro, NSP7/8/12, NSP7/8/12 +RNA, NSP15, NSP16, Spike, Spike+ACE).	Curcumin	29-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	178-187
35390745-9	2022	Our results suggested that isoskimmiwallin and terflavin A are potential inhibitors of RdRp, whereas isoquercitrin and isoorientin are the lead molecules against Mpro.	terflavin A	47-58	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	87-91
35259661-6	2022	In the molecular docking studies, the best binding scores for the 22 proposed curcumin derivatives were obtained for the PLpro protein.	Curcumin	78-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	121-126
35596627-7	2022	Mapping the activity of silibinin indicated its excellent binding inhibition activity against SARS-CoV-2 S protein, Mpro and RdRP at IC50 0.029, 0.021, and 0.042 muM, respectively, while it showed no inhibition activity against TMPRSS2 at its IC50(SARS-CoV-2) .	Silybin	24-33	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	125-129
35622909-1	2022	The nonstructural protein 3 (NSP3) macrodomain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Mac1) removes adenosine diphosphate (ADP) ribosylation posttranslational modifications, playing a key role in the immune evasion capabilities of the virus responsible for the coronavirus disease 2019 pandemic.	Adenosine	126-135	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	29-33
35622909-1	2022	The nonstructural protein 3 (NSP3) macrodomain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Mac1) removes adenosine diphosphate (ADP) ribosylation posttranslational modifications, playing a key role in the immune evasion capabilities of the virus responsible for the coronavirus disease 2019 pandemic.	Adenosine Diphosphate	149-152	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	29-33
35622909-2	2022	Here, we determined neutron and x-ray crystal structures of the SARS-CoV-2 NSP3 macrodomain using multiple crystal forms, temperatures, and pHs, across the apo and ADP-ribose-bound states.	Adenosine Diphosphate	164-167	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	75-79
35622909-2	2022	Here, we determined neutron and x-ray crystal structures of the SARS-CoV-2 NSP3 macrodomain using multiple crystal forms, temperatures, and pHs, across the apo and ADP-ribose-bound states.	Ribose	168-174	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	75-79
35435671-2	2022	Remdesivir is a nucleotide analogue that targets the RNA-dependent RNA polymerase (RdRp) of coronaviruses, including SARS-CoV-2.	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	83-87
35435671-4	2022	Several hypotheses of the mechanism of inhibition of RdRp by remdesivir have been proposed, although open questions remain.	remdesivir	61-71	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	53-57
35435671-5	2022	This work uses molecular dynamics simulations to explore the impact of remdesivir and two analogues as incoming nucleotides and of up to four incorporations of remdesivir along the primer strand on RdRp.	remdesivir	71-81	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	198-202
35435671-5	2022	This work uses molecular dynamics simulations to explore the impact of remdesivir and two analogues as incoming nucleotides and of up to four incorporations of remdesivir along the primer strand on RdRp.	remdesivir	160-170	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	198-202
35435671-6	2022	The simulation results suggest that the overall structure and the dynamical behavior of RdRp are destabilized by remdesivir and the two analogues in the incoming position.	remdesivir	113-123	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	88-92
35435671-7	2022	The incorporation of remdesivir along the primer strand impacts specific non-bonded interactions between the nascent RNA and the polymerase subunit, as well as the overall dynamical networks on RdRp.	remdesivir	21-31	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	194-198
35435671-9	2022	Our results provide atomic-level details of the role played by remdesivir on the disruption of RNA synthesis by RdRp and the main drivers of these disruptions.	remdesivir	63-73	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	112-116
35596627-10	2022	Comparative molecular docking (MD) showed that silibinin possesses the highest binding affinity to S protein and RdRP at -7.78 and -7.15 kcal/mol, respectively.	Silybin	47-56	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	113-117
35021060-3	2022	Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PLpro) inhibitor.	Acriflavine	45-56	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	97-102
35021060-3	2022	Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PLpro) inhibitor.	Acriflavine	58-61	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	97-102
35021060-4	2022	NMR titrations and a co-crystal structure confirm that acriflavine blocks the PLpro catalytic pocket in an unexpected binding mode.	Acriflavine	55-66	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	78-83
35465139-2	2022	Our study analyzes the binding mode of both natural triphosphate substrates as well as remdesivir triphosphate (the active form of drug), which is bound preferentially over ATP by RdRp while being poorly recognized by human RNA polymerase II (RNA Pol II).	triphosphoric acid	52-64	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	180-184
35465139-2	2022	Our study analyzes the binding mode of both natural triphosphate substrates as well as remdesivir triphosphate (the active form of drug), which is bound preferentially over ATP by RdRp while being poorly recognized by human RNA polymerase II (RNA Pol II).	remdesivir	87-97	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	180-184
35465139-2	2022	Our study analyzes the binding mode of both natural triphosphate substrates as well as remdesivir triphosphate (the active form of drug), which is bound preferentially over ATP by RdRp while being poorly recognized by human RNA polymerase II (RNA Pol II).	Adenosine Triphosphate	173-176	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	180-184
35625907-0	2022	Natural Polyphenols, 1,2,3,4,6-O-Pentagalloyglucose and Proanthocyanidins, as Broad-Spectrum Anticoronaviral Inhibitors Targeting Mpro and RdRp of SARS-CoV-2.	Polyphenols	8-19	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	139-143
35625907-0	2022	Natural Polyphenols, 1,2,3,4,6-O-Pentagalloyglucose and Proanthocyanidins, as Broad-Spectrum Anticoronaviral Inhibitors Targeting Mpro and RdRp of SARS-CoV-2.	1,2,3,4,6-o-pentagalloyglucose	21-51	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	139-143
35625907-0	2022	Natural Polyphenols, 1,2,3,4,6-O-Pentagalloyglucose and Proanthocyanidins, as Broad-Spectrum Anticoronaviral Inhibitors Targeting Mpro and RdRp of SARS-CoV-2.	Proanthocyanidins	56-73	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	139-143
35625907-6	2022	The effects of PGG and PAC on the activity of the other essential SARS-CoV-2 viral protein, RdRp, were analyzed using a cell-based activity assay system.	pgg	15-18	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	92-96
35625907-6	2022	The effects of PGG and PAC on the activity of the other essential SARS-CoV-2 viral protein, RdRp, were analyzed using a cell-based activity assay system.	proanthocyanidin	23-26	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	92-96
35625907-7	2022	The activity of RdRp is inhibited by PGG and PAC, and PGG has a lower IC50 (5.098 +- 1.089 muM) than PAC (21.022 +- 1.202 muM), which is consistent with their inhibitory capacity of SARS-CoV-2 infection.	pgg	37-40	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	16-20
35625907-7	2022	The activity of RdRp is inhibited by PGG and PAC, and PGG has a lower IC50 (5.098 +- 1.089 muM) than PAC (21.022 +- 1.202 muM), which is consistent with their inhibitory capacity of SARS-CoV-2 infection.	proanthocyanidin	45-48	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	16-20
35625907-7	2022	The activity of RdRp is inhibited by PGG and PAC, and PGG has a lower IC50 (5.098 +- 1.089 muM) than PAC (21.022 +- 1.202 muM), which is consistent with their inhibitory capacity of SARS-CoV-2 infection.	proanthocyanidin	101-104	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	16-20
35625907-9	2022	These data indicate that PGG and PAC may be candidate broad-spectrum anticoronaviral therapeutic agents, simultaneously targeting the Mpro and RdRp proteins of SARS-CoV-2.	proanthocyanidin	33-36	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	143-147
35551511-6	2022	We identified three main roles for NSP6: to act as a filter in RO-ER communication allowing lipid flow but restricting access of ER luminal proteins to the DMVs, to position and organize DMV clusters, and to mediate contact with lipid droplets (LDs) via the LD-tethering complex DFCP1-Rab18.	Phenobarbital	132-139	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	35-39
35503748-1	2022	Inhibition of RNA-dependent RNA polymerase (RdRp) by nucleotide analogues with ribose modification provides a promising antiviral strategy for the treatment of SARS-CoV-2.	Ribose	79-85	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	44-48
35634324-2	2022	Remdesivir inhibits viral RdRp, controls the multiplication of the virus, and protects patients.	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	26-30
35634324-9	2022	Simultaneously, remdesivir and baricitinib as a combination inhibit their target viral RdRp and human Janus kinase, respectively.	remdesivir	16-26	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	87-91
35634324-9	2022	Simultaneously, remdesivir and baricitinib as a combination inhibit their target viral RdRp and human Janus kinase, respectively.	baricitinib	31-42	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	87-91
35551511-6	2022	We identified three main roles for NSP6: to act as a filter in RO-ER communication allowing lipid flow but restricting access of ER luminal proteins to the DMVs, to position and organize DMV clusters, and to mediate contact with lipid droplets (LDs) via the LD-tethering complex DFCP1-Rab18.	(2R,3R)-2,3-dihydroxy-3-methylpentanoic acid	187-190	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	35-39
35551511-7	2022	NSP6 thus acts as an organizer of DMV clusters and can provide a selective track to refurbish them with LD-derived lipids.	(2R,3R)-2,3-dihydroxy-3-methylpentanoic acid	34-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	0-4
35510619-0	2022	25 (S)-Hydroxycholesterol acts as a possible dual enzymatic inhibitor of SARS-CoV-2 Mpro and RdRp-: an insight from molecular docking and dynamics simulation approaches.	Hydroxycholesterols	3-25	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	93-97
35085423-6	2022	Less selective M pro inhibitors, e.g. auranofin, inhibit PL pro , highlighting the potential for dual PL pro /M pro inhibition.	Auranofin	38-47	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	57-63
35578732-7	2022	Serendipitously, PGG was found to inhibit the SARS-CoV-2 PLpro with an IC50 of 3.90 microM.	beta-penta-O-galloyl-glucose	17-20	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	57-62
35578732-9	2022	However, PGG was cytotoxic in 293T-ACE2 cells (CC50 = 7.7 microM), so its intracellular PLpro inhibitory activity could not be quantified by the cell-based Flip-GFP PLpro assay.	beta-penta-O-galloyl-glucose	9-12	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	88-93
35578732-10	2022	In addition, we also invalidated ebselen, disulfiram, carmofur, PX12, and tideglusib as SARS-CoV-2 PLpro inhibitors using the Flip-GFP assay.	ebselen	33-40	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-104
35578732-10	2022	In addition, we also invalidated ebselen, disulfiram, carmofur, PX12, and tideglusib as SARS-CoV-2 PLpro inhibitors using the Flip-GFP assay.	Disulfiram	42-52	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-104
35578732-10	2022	In addition, we also invalidated ebselen, disulfiram, carmofur, PX12, and tideglusib as SARS-CoV-2 PLpro inhibitors using the Flip-GFP assay.	carmofur	54-62	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-104
35578732-11	2022	Overall, our results call for stringent hit validation, and the serendipitous discovery of PGG as a putative PLpro inhibitor might worth further pursuing.	beta-penta-O-galloyl-glucose	91-94	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	109-114
35538380-9	2022	MC interacted with critical residues of NSP3 macro-domain and NSP10-NSP16 complex and occupied their active sites.	Methylcholanthrene	0-2	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	40-44
35538380-9	2022	MC interacted with critical residues of NSP3 macro-domain and NSP10-NSP16 complex and occupied their active sites.	Methylcholanthrene	0-2	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	62-67
35602049-3	2022	In the current study, we predicted that doxycycline could interact with the nucleotide triphosphate (NTP) entry channel, and is therefore expected to hinder the viral replication of SARS-CoV-2 RNA-dependent RNA-polymerase (RdRp) through docking analysis.	Doxycycline	40-51	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	223-227
35602049-3	2022	In the current study, we predicted that doxycycline could interact with the nucleotide triphosphate (NTP) entry channel, and is therefore expected to hinder the viral replication of SARS-CoV-2 RNA-dependent RNA-polymerase (RdRp) through docking analysis.	nucleotide triphosphate	76-99	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	223-227
35602049-3	2022	In the current study, we predicted that doxycycline could interact with the nucleotide triphosphate (NTP) entry channel, and is therefore expected to hinder the viral replication of SARS-CoV-2 RNA-dependent RNA-polymerase (RdRp) through docking analysis.	ntp	101-104	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	223-227
35602049-4	2022	Further, the molecular dynamics results revealed that the RdRp-Doxycycline complex was structurally relatively stable during the dynamic period (100 ns), and its complex maintained close contact with their active catalytic domains of SARS-CoV-2 RdRp.	Doxycycline	63-74	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	58-62
35602049-4	2022	Further, the molecular dynamics results revealed that the RdRp-Doxycycline complex was structurally relatively stable during the dynamic period (100 ns), and its complex maintained close contact with their active catalytic domains of SARS-CoV-2 RdRp.	Doxycycline	63-74	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	245-249
35602049-5	2022	The molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculation of binding free energy also showed that the doxycycline has worthy affinities with SARS-CoV-2 RdRp.	Doxycycline	121-132	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	171-175
35185356-8	2022	The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection.	Ribavirin	50-59	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	38-42
35403090-10	2022	In silico data suggest that TFMG significantly blocked the entry, exit, and amino acids at catalytic active-site of more than thirty proteins including viral (nsp1,nsp2,Mainpro,~-9.0 kcal/mol) and host inflammatory, oxidants, apoptotic, vaso-destabilizer molecules (FAS, CD40R, BCL2, TLR2, ~ -10 and ACE1or2 ~ -9.0 and AT1or2~ -7.5 kcal/mol and more).	tfmg	28-32	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	164-168
35233172-4	2022	Based on binding affinity, dynamics behavior, and binding free energies, the present study identifies pentaoxahexacyclo-dotriacontanonaen-trihydroxybenzoate derivative (PDT), rutin, and dihyroxy-oxan-phenyl-chromen-4-one derivative (DOC), luteolin-7-glucoside-4"-neohesperidoside as promising inhibitors of SARS-CoV-2 Mpro and PLpro, respectively.	Luteolin 7-glucoside-4'-neohesperidoside	239-279	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	327-332
35185356-8	2022	The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection.	Ribavirin	50-59	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	173-177
35185356-8	2022	The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection.	remdesivir	61-71	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	38-42
35185356-8	2022	The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection.	remdesivir	61-71	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	173-177
35185356-8	2022	The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection.	Sofosbuvir	73-83	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	38-42
35185356-8	2022	The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection.	Sofosbuvir	73-83	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	173-177
35185356-8	2022	The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection.	galidesivir	85-96	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	38-42
35185356-8	2022	The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection.	galidesivir	85-96	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	173-177
35185356-8	2022	The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection.	Tenofovir	102-111	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	38-42
35185356-8	2022	The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection.	Tenofovir	102-111	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	173-177
35185356-9	2022	RdRp inhibitors, such as remdesivir (an anti-Ebola virus experimental drug) and favipiravir (an anti-influenza drug), inhibit RdRp and thus slow the progression of COVID-19 and associated clinical symptoms, as well as significantly shorten recovery time.	remdesivir	25-35	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	0-4
35185356-9	2022	RdRp inhibitors, such as remdesivir (an anti-Ebola virus experimental drug) and favipiravir (an anti-influenza drug), inhibit RdRp and thus slow the progression of COVID-19 and associated clinical symptoms, as well as significantly shorten recovery time.	remdesivir	25-35	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-130
35185356-9	2022	RdRp inhibitors, such as remdesivir (an anti-Ebola virus experimental drug) and favipiravir (an anti-influenza drug), inhibit RdRp and thus slow the progression of COVID-19 and associated clinical symptoms, as well as significantly shorten recovery time.	favipiravir	80-91	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	0-4
35185356-9	2022	RdRp inhibitors, such as remdesivir (an anti-Ebola virus experimental drug) and favipiravir (an anti-influenza drug), inhibit RdRp and thus slow the progression of COVID-19 and associated clinical symptoms, as well as significantly shorten recovery time.	favipiravir	80-91	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	126-130
35185356-10	2022	Molnupiravir, an orally active RdRp inhibitor and noval broad spectrum antiviral agent, is an isopropyl pro-drug of EIDD-1931 for emergency use.	EIDD 2801	0-12	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	31-35
35233172-4	2022	Based on binding affinity, dynamics behavior, and binding free energies, the present study identifies pentaoxahexacyclo-dotriacontanonaen-trihydroxybenzoate derivative (PDT), rutin, and dihyroxy-oxan-phenyl-chromen-4-one derivative (DOC), luteolin-7-glucoside-4"-neohesperidoside as promising inhibitors of SARS-CoV-2 Mpro and PLpro, respectively.	pentaoxahexacyclo-dotriacontanonaen-trihydroxybenzoate	102-156	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	327-332
35233172-4	2022	Based on binding affinity, dynamics behavior, and binding free energies, the present study identifies pentaoxahexacyclo-dotriacontanonaen-trihydroxybenzoate derivative (PDT), rutin, and dihyroxy-oxan-phenyl-chromen-4-one derivative (DOC), luteolin-7-glucoside-4"-neohesperidoside as promising inhibitors of SARS-CoV-2 Mpro and PLpro, respectively.	Rutin	175-180	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	327-332
35547854-0	2022	Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1.	omicron ba	40-50	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	8-14
35624740-7	2022	The literature reveals that quercetin exhibits anti-COVID-19 activity because of its inhibitory effect on the expression of the human ACE2 receptors and the enzymes of SARS-CoV-2 (MPro, PLPro, and RdRp).	Quercetin	28-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	197-201
35420322-6	2022	Meanwhile, all the tested AGP derivatives showed a better binding score with RdRp and S than remdesivir (REM).	andrographolide	26-29	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	77-81
35566148-6	2022	Concerning SARS-CoV-2 PLpro, cannabichromanon (32) followed by cannabinolic acid (22) and cannabicyclolic acid (41) revealed the best binding within its active pockets owing to multiple bond formation with  G values of -28.36, -22.81, and -19.89 kcal/mol.	UNII-CVK7769BHC	29-45	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	22-27
35566148-6	2022	Concerning SARS-CoV-2 PLpro, cannabichromanon (32) followed by cannabinolic acid (22) and cannabicyclolic acid (41) revealed the best binding within its active pockets owing to multiple bond formation with  G values of -28.36, -22.81, and -19.89 kcal/mol.	cannabinolic acid	63-80	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	22-27
35566148-6	2022	Concerning SARS-CoV-2 PLpro, cannabichromanon (32) followed by cannabinolic acid (22) and cannabicyclolic acid (41) revealed the best binding within its active pockets owing to multiple bond formation with  G values of -28.36, -22.81, and -19.89 kcal/mol.	Cannabicyclolic acid	90-110	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	22-27
35341301-5	2022	The Beta and Delta variants adversely affected the analytical sensitivity of the BioGerm ORF1ab gene assay (9.52% versus 42.96%, P = 0.014, and 14.29% versus 42.96%, P = 0.040, respectively), whereas the N gene assay completely failed in terms of the Fin-796H variant.	796h	255-259	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	89-95
35181310-4	2022	Effect of 2-DG on virus multiplication was evaluated by RT-PCR (N and RdRp genes) analysis, protein expression analysis of Nucleocapsid (N) and Spike (S) proteins and visual indication of cytopathy effect (CPE), The mass spectrometry analysis was performed to examine the 2-DG induced change in glycosylation status of receptor binding domain (RBD) in SARS-CoV-2 spike protein.	Deoxyglucose	10-14	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	70-74
35430987-8	2022	Favipiravir is effective against SARS-CoV-2 infection through inhibition of RdRp.	favipiravir	0-11	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	76-80
35482820-6	2022	Two lineages encoded the S759A substitution at the RdRp Ser759-Asp-Asp active motif.	aspartyl-aspartic acid	63-70	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	51-55
35482820-9	2022	Biochemical analysis of SARS-CoV-2 RdRp encoding S759A demonstrated a roughly 10-fold decreased preference for RDV-triphosphate (RDV-TP) as a substrate, whereas nsp12-V792I diminished the uridine-triphosphate (UTP) concentration needed to overcome template-dependent inhibition associated with RDV.	remdesivir	111-114	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	35-39
35482820-9	2022	Biochemical analysis of SARS-CoV-2 RdRp encoding S759A demonstrated a roughly 10-fold decreased preference for RDV-triphosphate (RDV-TP) as a substrate, whereas nsp12-V792I diminished the uridine-triphosphate (UTP) concentration needed to overcome template-dependent inhibition associated with RDV.	remdesivir	129-132	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	35-39
35566014-6	2022	The other ligands, namely chicoric acid, demothoxycurcumin, and curcumin express high binding energy than the other tested ligands docked to PLpro with -7.62, -6.81, and -6.70 kcal/mol, respectively.	chicoric acid	26-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	141-146
35566014-6	2022	The other ligands, namely chicoric acid, demothoxycurcumin, and curcumin express high binding energy than the other tested ligands docked to PLpro with -7.62, -6.81, and -6.70 kcal/mol, respectively.	demothoxycurcumin	41-58	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	141-146
35566014-6	2022	The other ligands, namely chicoric acid, demothoxycurcumin, and curcumin express high binding energy than the other tested ligands docked to PLpro with -7.62, -6.81, and -6.70 kcal/mol, respectively.	Curcumin	64-72	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	141-146
35464436-4	2022	Nucleotide analogs (NAs), such as remdesivir, is the most promising class of RdRp inhibitors to be used in the treatment of COVID-19.	remdesivir	34-44	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	77-81
35494659-0	2022	Insights Into Drug Repurposing, as Well as Specificity and Compound Properties of Piperidine-Based SARS-CoV-2 PLpro Inhibitors.	piperidine	82-92	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	110-115
35494659-6	2022	We also report our latest efforts to improve piperidine-scaffold inhibitors, 5c and 3k, originally developed for SARS-CoV PLpro.	piperidine	45-55	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	122-127
35480391-4	2022	Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of PLpro for ubiquitin and ISG15.	Hydrazones	40-49	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	157-162
35480391-4	2022	Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of PLpro for ubiquitin and ISG15.	Thiosemicarbazones	64-81	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	157-162
35480391-5	2022	H1 binds to a polar groove at the S1 binding site by forming several hydrogen bonds with PLpro.	Hydrogen	69-77	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	89-94
35480391-11	2022	In combination with the inexpensive and undemanding synthesis, the reported hydrazone and thiosemicarbazones represent an attractive scaffold for further structure-based development of novel PLpro inhibitors by interrupting protein-protein interactions at the S1 and S2 site.	Hydrazones	76-85	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	191-196
35480391-11	2022	In combination with the inexpensive and undemanding synthesis, the reported hydrazone and thiosemicarbazones represent an attractive scaffold for further structure-based development of novel PLpro inhibitors by interrupting protein-protein interactions at the S1 and S2 site.	Thiosemicarbazones	90-108	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	191-196
35539693-3	2022	In this work, we report a highly sequence-specific biosensor based on nanocomposites with aggregation-induced emission luminogens (AIEgen)-labeled oligonucleotide probes on graphene oxide nanosheets (AIEgen@GO) for one step-detection of SARS-CoV-2-specific nucleic acid sequences (Orf1ab or N genes).	Oligonucleotides	147-162	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	281-287
35539693-3	2022	In this work, we report a highly sequence-specific biosensor based on nanocomposites with aggregation-induced emission luminogens (AIEgen)-labeled oligonucleotide probes on graphene oxide nanosheets (AIEgen@GO) for one step-detection of SARS-CoV-2-specific nucleic acid sequences (Orf1ab or N genes).	graphene oxide	173-187	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	281-287
35464436-8	2022	An in vitro RdRp activity assay has been established with a reconstituted nsp12/nsp7/nsp8 complex and biotin-labeled self-priming RNAs, and the activity of the RdRp complex was determined by detecting binding and extension of RNAs.	Biotin	102-108	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	12-16
35464436-10	2022	We demonstrated that the active triphosphate form of remdesivir (RTP) and several reported non-nucleotide analog viral polymerase inhibitors blocked the RdRp in the in vitro RdRp activity assay and high-throughput screening model.	triphosphoric acid	32-44	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	153-157
35464436-10	2022	We demonstrated that the active triphosphate form of remdesivir (RTP) and several reported non-nucleotide analog viral polymerase inhibitors blocked the RdRp in the in vitro RdRp activity assay and high-throughput screening model.	triphosphoric acid	32-44	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-178
35464436-10	2022	We demonstrated that the active triphosphate form of remdesivir (RTP) and several reported non-nucleotide analog viral polymerase inhibitors blocked the RdRp in the in vitro RdRp activity assay and high-throughput screening model.	remdesivir	53-63	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	153-157
35464436-10	2022	We demonstrated that the active triphosphate form of remdesivir (RTP) and several reported non-nucleotide analog viral polymerase inhibitors blocked the RdRp in the in vitro RdRp activity assay and high-throughput screening model.	remdesivir	53-63	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-178
35384604-7	2022	Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position.	4-Fluorobenzoyl chloride	101-106	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	148-153
35384604-7	2022	Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position.	4-Fluorobenzoyl chloride	101-106	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	240-245
35185264-4	2022	Recent studies have identified a sulfur (S) metal-binding site in the zinc center structures of the RdRp complex.	Metals	44-49	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	100-104
35438554-11	2022	Molecular docking showed that the active components of HCT (quercetin and kaempferol) had similar binding affinities for SARS-CoV-2 3CLpro and SARS-CoV-2 RdRp, primary COVID-19 target proteins as did clinically used drugs.	Quercetin	60-69	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	154-158
35185264-4	2022	Recent studies have identified a sulfur (S) metal-binding site in the zinc center structures of the RdRp complex.	Sulfur	33-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	100-104
35185264-8	2022	l-Methionine can operate as a carrier, and its binding would cause the potential disassembly of RdRp via the S complex and drive methyl donors via a possible countercurrent exchange mechanism and electrical-chemical gradient leading to SARS-CoV-2 replication failure.	Methionine	0-12	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	96-100
35185264-10	2022	The S binding site in l-Methionine serves as a potential target cofactor for SARS-CoV RdRp, thus providing a possible avenue for the future development of vaccines and antiviral therapeutic strategies to combat COVID-19.	Methionine	22-34	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	86-90
35378761-9	2022	However, PGG was cytotoxic in 293T-ACE2 cells (CC 50 = 7.7 microM), so its intracellular PL pro inhibitory activity could not be quantified by the cell-based Flip-GFP PL pro assay.	beta-penta-O-galloyl-glucose	9-12	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	89-95
35378761-10	2022	In addition, we also invalidated ebselen, disulfiram, carmofur, PX12, and tideglusib as SARS-CoV-2 PL pro inhibitors using the Flip-GFP assay.	ebselen	33-40	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-105
35378761-10	2022	In addition, we also invalidated ebselen, disulfiram, carmofur, PX12, and tideglusib as SARS-CoV-2 PL pro inhibitors using the Flip-GFP assay.	Disulfiram	42-52	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-105
35378761-10	2022	In addition, we also invalidated ebselen, disulfiram, carmofur, PX12, and tideglusib as SARS-CoV-2 PL pro inhibitors using the Flip-GFP assay.	carmofur	54-62	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	99-105
35378761-11	2022	Overall, our results call for stringent hit validation, and the serendipitous discovery of PGG as a putative PL pro inhibitor might worth further pursuing.	beta-penta-O-galloyl-glucose	91-94	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	109-115
35351926-7	2022	Three drugs-amprenavir, levomefolic acid, and calcipotriol-were predicted to bind to 3 different sites on the spike protein, domperidone to the Mac1 domain of the non-structural protein (Nsp) 3, avanafil to Nsp15, and nintedanib to the nucleocapsid protein involved in packaging the viral RNA.	amprenavir	12-22	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	163-193
35351926-7	2022	Three drugs-amprenavir, levomefolic acid, and calcipotriol-were predicted to bind to 3 different sites on the spike protein, domperidone to the Mac1 domain of the non-structural protein (Nsp) 3, avanafil to Nsp15, and nintedanib to the nucleocapsid protein involved in packaging the viral RNA.	5-methyltetrahydrofolate	24-40	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	163-193
35337173-6	2022	Four spiro(indoline-3,5"-pyrido(2,3-d:6,5-d")dipyrimidine derivatives 3a, 4b, 4d, and 4e showed high activities against the SARS-CoV-2 in plaque reduction assay and were subjected to further RNA-dependent-RNA-polymerase (RdRp) and spike glycoprotein inhibition assay investigations.	spiro(indoline-3,5"-pyrido(2,3-d:6,5-d")dipyrimidine	5-57	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	221-225
35351926-7	2022	Three drugs-amprenavir, levomefolic acid, and calcipotriol-were predicted to bind to 3 different sites on the spike protein, domperidone to the Mac1 domain of the non-structural protein (Nsp) 3, avanafil to Nsp15, and nintedanib to the nucleocapsid protein involved in packaging the viral RNA.	calcipotriene	46-58	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	163-193
35351926-7	2022	Three drugs-amprenavir, levomefolic acid, and calcipotriol-were predicted to bind to 3 different sites on the spike protein, domperidone to the Mac1 domain of the non-structural protein (Nsp) 3, avanafil to Nsp15, and nintedanib to the nucleocapsid protein involved in packaging the viral RNA.	Domperidone	125-136	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	163-193
35337173-7	2022	The four compounds exhibited potent inhibitory activity ranging from 40.23 +- 0.09 to 44.90 +- 0.08 nM and 40.27 +- 0.17 to 44.83 +- 0.16 nM, respectively, when compared with chloroquine as a reference standard, which showed 45 +- 0.02 and 45 +- 0.06 nM against RdRp and spike glycoprotein, respectively.	Chloroquine	175-186	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	262-266
35227055-5	2022	Results: Theaflavin and catechin, the natural components of black tea and green tea, out of 10 shortlisted compounds have shown excellent performance in our docking studies with the minimum binding energy of -11.8 kcal/mol and -9.2 kcal/mol respectively, against a novel nsp10-nsp16 complex of SARS-CoV-2 that indicates their potential for inhibitory molecular interactions against the virus to assist rapid drug designing from natural products.	theaflavin	9-19	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	271-276
35199520-7	2022	We find evidence that the viral poly(A) template binds similarly to the template strand of the P/T RNA duplex within the RTC, mainly through electrostatic interactions, providing new insights into the priming reaction by the nsp8 subunit within the RTC, which differs significantly from the existing proposal of the nsp7/nsp8 oligomer formed outside the RTC.	Poly A	32-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	225-229
35199520-7	2022	We find evidence that the viral poly(A) template binds similarly to the template strand of the P/T RNA duplex within the RTC, mainly through electrostatic interactions, providing new insights into the priming reaction by the nsp8 subunit within the RTC, which differs significantly from the existing proposal of the nsp7/nsp8 oligomer formed outside the RTC.	Poly A	32-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	316-320
35199520-7	2022	We find evidence that the viral poly(A) template binds similarly to the template strand of the P/T RNA duplex within the RTC, mainly through electrostatic interactions, providing new insights into the priming reaction by the nsp8 subunit within the RTC, which differs significantly from the existing proposal of the nsp7/nsp8 oligomer formed outside the RTC.	Poly A	32-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	321-325
35184550-7	2022	To demonstrate the advantageous features of the TFME platform, a customized leuco crystal violet LAMP assay is used for visual detection of the ORF1ab DNA sequence from SARS-CoV-2 spiked into artificial oral fluid samples.	leucocrystal violet	76-96	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	144-150
35262078-1	2022	A series of amino acid based 7H -pyrrolo(2,3- d )pyrimidines were designed and synthesized to discern the structure activity relationships against the SARS-CoV-2 nsp3 macrodomain (Mac1), an ADP-ribosylhydrolase that is critical for coronavirus replication and pathogenesis.	7h -pyrrolo(2,3- d )pyrimidines	29-60	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	162-166
35369500-3	2022	The interaction of atorvastatin with RdRp (RNA-dependent RNA polymerase) and 3CL protease (3-chymotrypsin-like protease) was evaluated by molecular docking.	Atorvastatin	19-31	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	37-41
35369500-8	2022	The interaction of atorvastatin with SARS-CoV-2 RdRp and 3CL protease yielded a binding affinity of -6.7 kcal/mol and -7.5 kcal/mol, respectively.	Atorvastatin	19-31	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	48-52
35253618-4	2022	Among the algal compounds screened in this study, three (Laminarin, Astaxanthin and 4"-chlorostypotriol triacetate) exhibited the lowest docking energy and best interaction with SARS-CoV-2 viral proteins (Main protease, RdRp, Nsp15, and spike protein).	laminaran	57-66	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	220-224
35253618-4	2022	Among the algal compounds screened in this study, three (Laminarin, Astaxanthin and 4"-chlorostypotriol triacetate) exhibited the lowest docking energy and best interaction with SARS-CoV-2 viral proteins (Main protease, RdRp, Nsp15, and spike protein).	astaxanthine	68-79	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	220-224
35253618-4	2022	Among the algal compounds screened in this study, three (Laminarin, Astaxanthin and 4"-chlorostypotriol triacetate) exhibited the lowest docking energy and best interaction with SARS-CoV-2 viral proteins (Main protease, RdRp, Nsp15, and spike protein).	4'-Chlorostypotriol triacetate	84-114	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	220-224
35227055-5	2022	Results: Theaflavin and catechin, the natural components of black tea and green tea, out of 10 shortlisted compounds have shown excellent performance in our docking studies with the minimum binding energy of -11.8 kcal/mol and -9.2 kcal/mol respectively, against a novel nsp10-nsp16 complex of SARS-CoV-2 that indicates their potential for inhibitory molecular interactions against the virus to assist rapid drug designing from natural products.	Catechin	24-32	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	271-276
35037045-8	2022	Using our developed assays, we identify drug and drug-like molecules that inhibit nsp14-nsp10, including the known SARS-CoV-2 major protease (Mpro) inhibitor ebselen and the HIV integrase inhibitor raltegravir, revealing the potential for multifunctional inhibitors in COVID-19 treatment.	Raltegravir Potassium	198-209	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	88-93
35193136-4	2022	METHOD: We utilized a nanomaterial-based optical sensing platform to detect RNA-dependent RNA polymerase (RdRp) gene of SARS-CoV-2, where the formation of oligo probe-target hybrid led to salt-induced aggregation and change in gold-colloid color from pink to blue visibility range.	Salts	188-192	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	106-110
35140265-5	2022	Our results indicate only aloin A and B effectively inhibited proteolytic activity of PLpro with an IC50 of 13.16 and 16.08 muM.	aloin a and b	26-39	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	86-91
35189369-2	2022	Thus, herein, we present an overview of ribonucleoside analogs recently developed and acting as inhibitors of the viral RNA-dependent RNA polymerase (RdRp).	Ribonucleosides	40-54	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	150-154
35224406-0	2022	Binding Studies of the Prodrug HAO472 to SARS-Cov-2 Nsp9 and Variants.	HAO472	31-37	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	52-56
35224406-2	2022	In a previous screen of a natural product library against purified SARS-CoV-2 Nsp9 using a native mass spectrometry-based approach, we identified an ent-kaurane natural product, oridonin (1), with micromolar affinities.	oridonin	178-186	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	78-82
35224406-3	2022	In this work, we have found that the prodrug HAO472 (2) directly binds to Nsp9, establishing replacement of the labile ester with a bioisostere as a candidate drug strategy.	hao472 (2)	45-55	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	74-78
35224406-3	2022	In this work, we have found that the prodrug HAO472 (2) directly binds to Nsp9, establishing replacement of the labile ester with a bioisostere as a candidate drug strategy.	Esters	119-124	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	74-78
35152367-5	2022	Twenty different types of potent phlorotannins were targeted against druggable target proteins, viz., 3CLpro, RdRp, and Spro using AutoDock molecular docking, drug-likeness were assessed by ADMET profiling (QikProp module).	phlorotannins	33-46	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	110-114
35222340-7	2022	Our results showed that, among the identified potential drugs with anti-SARS-CoV-2 properties, Hypericin, an important component of the Hypericum perforatum that presents antiviral and antitumoral properties, binds with high affinity to viral Mpro and RdRp.	hypericin	95-104	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	252-256
35169801-2	2022	Here, we determined neutron and X-ray crystal structures of the SARS-CoV-2 NSP3 macrodomain using multiple crystal forms, temperatures, and pHs, across the apo and ADP-ribose-bound states.	Adenosine Diphosphate	164-167	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	75-79
35169801-2	2022	Here, we determined neutron and X-ray crystal structures of the SARS-CoV-2 NSP3 macrodomain using multiple crystal forms, temperatures, and pHs, across the apo and ADP-ribose-bound states.	Ribose	168-174	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	75-79
35140265-7	2022	Computational structural modelling of aloin A and B interaction with PLpro revealed that, both aloin isoforms form hydrogen bond with Tyr268 of PLpro, which is critical for their proteolytic activity.	Hydrogen	115-123	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	69-74
35140265-7	2022	Computational structural modelling of aloin A and B interaction with PLpro revealed that, both aloin isoforms form hydrogen bond with Tyr268 of PLpro, which is critical for their proteolytic activity.	Hydrogen	115-123	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	144-149
35140265-10	2022	In conclusion, the isoforms of aloin inhibit both proteolytic and the deubiquitinating activity of SARS-CoV-2 PLpro, suggesting potential in inhibiting the replication of SARS-CoV-2 virus.	alloin	31-36	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	110-115
35187337-7	2022	Based on previous reports of biofunctions of the indigenously synthesized imine derivatives, they are explored for their potential inhibition properties against two very crucial proteins (main protease (Mpro) and nonstructural protein 9 (NSP9)) of SARS-CoV-2.	Imines	74-79	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	238-242
35101534-6	2022	Four candidate compounds, Fludarabine Phosphate, Fludarabine, 6-Thio-20-Deoxyguanosine (6-Thio-dG), and 5-Iodotubercidin, exhibit remarkable potency in inhibiting SARS-CoV-2 RdRp.	fludarabine phosphate	26-47	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-178
35110538-3	2022	Once in cells, AT-527 is converted into its triphosphate form, AT-9010, that presumably targets the viral RNA-dependent RNA polymerase (RdRp, nsp12), for incorporation into viral RNA.	triphosphoric acid	44-56	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	136-140
35033572-2	2022	Remdesivir, a broad-spectrum inhibitor of the viral RNA-dependent RNA polymerase (RdRp), was extensively prescribed under emergency use authorization during the first 18 months of the COVID19 pandemic, before randomized controlled trials showed poor efficacy in hospitalized patients.	remdesivir	0-10	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	82-86
35033572-3	2022	RdRp mutations conferring resistance to remdesivir are well known from in vitro studies, and the huge SARS-CoV-2 sequencing effort during the ongoing COVID19 pandemic represents an unprecedented opportunity to assess emergence and fitness of antiviral resistance in vivo.	remdesivir	40-50	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	0-4
35101534-6	2022	Four candidate compounds, Fludarabine Phosphate, Fludarabine, 6-Thio-20-Deoxyguanosine (6-Thio-dG), and 5-Iodotubercidin, exhibit remarkable potency in inhibiting SARS-CoV-2 RdRp.	fludarabine	49-60	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-178
35101534-6	2022	Four candidate compounds, Fludarabine Phosphate, Fludarabine, 6-Thio-20-Deoxyguanosine (6-Thio-dG), and 5-Iodotubercidin, exhibit remarkable potency in inhibiting SARS-CoV-2 RdRp.	6-thio-20-deoxyguanosine	62-86	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-178
35101534-6	2022	Four candidate compounds, Fludarabine Phosphate, Fludarabine, 6-Thio-20-Deoxyguanosine (6-Thio-dG), and 5-Iodotubercidin, exhibit remarkable potency in inhibiting SARS-CoV-2 RdRp.	6-Thio-dG	88-97	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-178
35101534-6	2022	Four candidate compounds, Fludarabine Phosphate, Fludarabine, 6-Thio-20-Deoxyguanosine (6-Thio-dG), and 5-Iodotubercidin, exhibit remarkable potency in inhibiting SARS-CoV-2 RdRp.	5-iodotubercidin	104-120	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	174-178
35101534-7	2022	Among these four compounds, 5-Iodotubercidin exhibited the strongest inhibition upon SARS-CoV-2 RdRp, and was resistant to viral exoribonuclease activity, thus presenting the best antiviral activity against coronavirus from a different genus.	5-iodotubercidin	28-44	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	96-100
35101534-8	2022	Further study showed that the RdRp inhibitory activity of 5-Iodotubercidin is closely related to its capacity to inhibit adenosine kinase (ADK).	5-iodotubercidin	58-74	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	30-34
35164069-0	2022	Computational Analysis Reveals Monomethylated Triazolopyrimidine as a Novel Inhibitor of SARS-CoV-2 RNA-Dependent RNA Polymerase (RdRp).	triazolopyrimidine	46-64	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	130-134
35056878-0	2022	Nucleotide Analogues Bearing a C2" or C3"-Stereogenic All-Carbon Quaternary Center as SARS-CoV-2 RdRp Inhibitors.	Carbon	58-64	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	97-101
35178512-4	2022	Several compounds including YM155, cryptotanshinone, tanshinone I, dihydrotanshinone I, tanshinone IIA, SJB2-043, 6-thioguanine, and 6-mercaptopurine were recently identified as SARS-CoV-2 PLpro inhibitors through high-throughput screenings.	Mercaptopurine	133-149	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	189-194
35178512-6	2022	Collectively, our results showed that all compounds tested either did not show binding or led to denaturation of PLpro in the TSA binding assay, which might explain their weak enzymatic inhibition in the FRET assay.	trichostatin A	126-129	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	113-118
35425333-4	2022	This study utilizes combined molecular dynamics simulation and molecular docking to test novel guanosine derivatives against SARS-CoV-2 RdRp.	Guanosine	95-104	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	136-140
35425333-6	2022	The bulky moieties (hydroxyl or fluorated phenyl moieties) added to the 2" position of the ribose ring positively impacted the binding affinity to RdRp.	Ribose	91-97	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	147-151
35425333-8	2022	It offers new potential binders or blockers of RdRp that bind to the protein active site tighter than remdesivir.	remdesivir	102-112	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	47-51
34981929-4	2022	Here, we described a novel peptide-drug conjugate (PDC), in which GRL0617 was linked to a sulfonium-tethered peptide derived from PLpro-specific substrate LRGG.	Sulfonium	90-99	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	130-135
35125499-9	2022	This study showed DAPG as a potential bioactive molecule to act as an inhibitor for the PLpro thereby, DAPG can be used as potential inhibitor against SARS-CoV-2 and is potential drug candidate against COVID-19.	2,4-diacetylphloroglucinol	18-22	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	88-93
35000060-5	2022	Molecular docking of HCQ under physiological condition with spike protein, 3C-like protease (3CLpro), and RNA-dependent RNA polymerase (RdRp) of SARS-CoV2 showed - 8.52 kcal/mole binding score with RdRp, while the other two proteins showed relatively weaker binding affinity.	Hydroxychloroquine	21-24	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	136-140
35000060-5	2022	Molecular docking of HCQ under physiological condition with spike protein, 3C-like protease (3CLpro), and RNA-dependent RNA polymerase (RdRp) of SARS-CoV2 showed - 8.52 kcal/mole binding score with RdRp, while the other two proteins showed relatively weaker binding affinity.	Hydroxychloroquine	21-24	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	198-202
35000060-14	2022	Overall, this study proposes two key natural chemical moieties: (a) tetrazol and (b) phenylpyrazol that can be investigated as a potential chemical group to design inhibitors against SARS-CoV2 RdRp.	phenylpyrazol	85-98	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	193-197
35018373-0	2022	Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2.	Naphthoquinones	34-49	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	133-138
35008944-5	2022	Furthermore, molecular dynamics simulation showed a stable interaction of structure 6 in RNA-dependent RNA polymerase (RdRp) complex and a lower average atomic fluctuation than GS-441524, suggesting a well accommodation in the RdRp binding pocket.	GS-441524	177-186	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	119-123
35008944-5	2022	Furthermore, molecular dynamics simulation showed a stable interaction of structure 6 in RNA-dependent RNA polymerase (RdRp) complex and a lower average atomic fluctuation than GS-441524, suggesting a well accommodation in the RdRp binding pocket.	GS-441524	177-186	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	227-231
35125499-9	2022	This study showed DAPG as a potential bioactive molecule to act as an inhibitor for the PLpro thereby, DAPG can be used as potential inhibitor against SARS-CoV-2 and is potential drug candidate against COVID-19.	2,4-diacetylphloroglucinol	103-107	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	88-93
35103034-4	2022	The effective hydrogen and hydrophobic (alkyl, pi -sigma, pi - pi T shaped and pi -alkyl) interaction analysis reveals the four antivirals sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are supposed to be the most auspicious inhibitors against nsp10 of SARS-CoV-2.	Sespenine	139-148	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	258-263
35103034-4	2022	The effective hydrogen and hydrophobic (alkyl, pi -sigma, pi - pi T shaped and pi -alkyl) interaction analysis reveals the four antivirals sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are supposed to be the most auspicious inhibitors against nsp10 of SARS-CoV-2.	xiamycin C	150-160	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	258-263
35103034-4	2022	The effective hydrogen and hydrophobic (alkyl, pi -sigma, pi - pi T shaped and pi -alkyl) interaction analysis reveals the four antivirals sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are supposed to be the most auspicious inhibitors against nsp10 of SARS-CoV-2.	Xiamycin methyl ester	162-183	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	258-263
35103034-9	2022	The lead antiviral compounds sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are recommended as the most promising inhibitors against nsp10 of SARS-CoV-2 pathogenicity.	Sespenine	29-38	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	147-152
35103034-9	2022	The lead antiviral compounds sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are recommended as the most promising inhibitors against nsp10 of SARS-CoV-2 pathogenicity.	xiamycin C	40-50	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	147-152
35103034-9	2022	The lead antiviral compounds sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are recommended as the most promising inhibitors against nsp10 of SARS-CoV-2 pathogenicity.	Xiamycin methyl ester	52-73	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	147-152
35103034-9	2022	The lead antiviral compounds sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are recommended as the most promising inhibitors against nsp10 of SARS-CoV-2 pathogenicity.	xiamycin	79-89	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	147-152
34740719-7	2022	A mutation in RdRp of SARS-CoV-2, particularly the change of Pro-to Leu-at 323 resulted in the stabilization of the structure in BRA/CD1739-P4/2020.	Proline	61-65	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	14-18
34740719-7	2022	A mutation in RdRp of SARS-CoV-2, particularly the change of Pro-to Leu-at 323 resulted in the stabilization of the structure in BRA/CD1739-P4/2020.	Leucine	68-71	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	14-18
35252541-3	2022	Novel peptide drugs have shown promise in the treatment of numerous diseases and new research has established that nsp10 derived peptides can disrupt viral methyltransferase activity via interaction of nsp16.	Peptides	129-137	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	115-120
35475214-6	2022	The computational analysis demonstrated that vitamin B12 resulted in depicting suitable significant binding with furin, RNA dependent RNA polymerase (RdRp), Main proteases (Mpro), ORF3a and ORF7a and Vitamin D3 with spike protein and vitamin B9 with non structural protein 3 (NSP3).	Vitamin B 12	45-56	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	150-154
35475214-6	2022	The computational analysis demonstrated that vitamin B12 resulted in depicting suitable significant binding with furin, RNA dependent RNA polymerase (RdRp), Main proteases (Mpro), ORF3a and ORF7a and Vitamin D3 with spike protein and vitamin B9 with non structural protein 3 (NSP3).	Vitamin B 12	45-56	ORF1a polyprotein;ORF1ab polyprotein	Severe acute respiratory syndrome coronavirus 2	276-280