Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods

Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, Wang Q, Xu Y, Li M, Li X, Zheng M, Chen L, Li H

10.1016/j.apsb.2020.02.008

Research curated

Abstract

SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Aspartame
Oxprenolol
Acetophenazine
Iopromide
Reproterol
Chloramphenicol
Chlorphenesin carbamate
Levodropropizine
Cefamandole
Tigecycline
Pemetrexed
Glutathione
Hesperetin
Masoprocol
Dantrolene
Sulfasalazine
Nicardipine
Sildenafil
Chrysin
Piceatannol
Alfuzosin
Cilastatin
Almitrine
Progabide
Nepafenac
Demeclocycline
Mimosine
Flavin mononucleotide
Lutein
Candoxatril
Estradiol valerate
Pioglitazone
Hesperidin
Novobiocin
chenodeoxycholic acid
Pancuronium	pancuronium bromide
Dabigatran etexilate
Ceftibuten
Fenoterol
Cefuroxime
Tibolone
Diphenoxylate
canrenoic acid
Ademetionine	Ademetionine, AdoMet, L-S-Adenosylmethionine, S-Adenosylmethionine, SAM
Rolitetracycline
Conivaptan
Famotidine
Helicase	Helicase, nsp13, Hel, p66, p66-HEL, Non-structural protein 13	rep, ORF1a-1b
Angiotensin-converting enzyme 2-Spike glycoprotein interface
Carvedilol
Chlorhexidine
Lymecycline
RNA dependent RNA polymerase	RDR, viral RNA polymerase, RdRp, nsp12	rep, ORF1a-1b, RdRp
Idarubicin
Bromocriptine
Oxytetracycline
Valganciclovir
Ribavirin	RBV, 1-beta-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide, 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide
Fosamprenavir
Saquinavir
Itraconazole
Cefsulodin
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Cefpiramide
Floxuridine
Fludarabine
Rutin
Pheneticillin
Telmisartan
Atovaquone
Riboflavin
Papain-like proteinases 1/2	Non-structural protein 3, papain like viral protease, nsp3, PL1-PRO/PL2-PRO, PLP1/PLP2, p195, Plpro	rep, ORF1a-1b
Doxycycline	Vibramycin
Montelukast
Isotretinoin	13-cis-retinoic acid

Related interactions

Target	Drug	Type	Result
Papain-like proteinases 1/2	Iopromide	Computational	positive
Papain-like proteinases 1/2	Aspartame	Computational	positive
Papain-like proteinases 1/2	Oxprenolol	Computational	positive
Papain-like proteinases 1/2	Doxycycline	Computational	positive
Papain-like proteinases 1/2	Acetophenazine	Computational	positive
Papain-like proteinases 1/2	Riboflavin	Computational	positive
Papain-like proteinases 1/2	Reproterol	Computational	positive
Papain-like proteinases 1/2	Chloramphenicol	Computational	positive
Papain-like proteinases 1/2	Chlorphenesin carbamate	Computational	positive
Papain-like proteinases 1/2	Levodropropizine	Computational	positive
Papain-like proteinases 1/2	Cefamandole	Computational	positive
Papain-like proteinases 1/2	Floxuridine	Computational	positive
Papain-like proteinases 1/2	Tigecycline	Computational	positive
Papain-like proteinases 1/2	Pemetrexed	Computational	positive
Papain-like proteinases 1/2	Glutathione	Computational	positive
Papain-like proteinases 1/2	Hesperetin	Computational	positive
Papain-like proteinases 1/2	Ademetionine	Computational	positive
Papain-like proteinases 1/2	Masoprocol	Computational	positive
Papain-like proteinases 1/2	Isotretinoin	Computational	positive
Papain-like proteinases 1/2	Dantrolene	Computational	positive
Papain-like proteinases 1/2	Sulfasalazine	Computational	positive
Papain-like proteinases 1/2	Nicardipine	Computational	positive
Papain-like proteinases 1/2	Sildenafil	Computational	positive
Papain-like proteinases 1/2	Chrysin	Computational	positive
Papain-like proteinases 1/2	Piceatannol	Computational	positive
3C-like protease	Alfuzosin	Computational	positive
3C-like protease	Cilastatin	Computational	positive
3C-like protease	Famotidine	Computational	positive
3C-like protease	Almitrine	Computational	positive
3C-like protease	Progabide	Computational	positive
3C-like protease	Nepafenac	Computational	positive
3C-like protease	Tigecycline	Computational	positive
3C-like protease	Demeclocycline	Computational	positive
3C-like protease	Mimosine	Computational	positive
3C-like protease	Flavin mononucleotide	Computational	positive
3C-like protease	Lutein	Computational	positive
3C-like protease	Pheneticillin	Computational	positive
3C-like protease	Candoxatril	Computational	positive
3C-like protease	Nicardipine	Computational	positive
3C-like protease	Estradiol valerate	Computational	positive
3C-like protease	Pioglitazone	Computational	positive
3C-like protease	Doxycycline	Computational	positive
RNA dependent RNA polymerase	Novobiocin	Computational	positive
RNA dependent RNA polymerase	chenodeoxycholic acid	Computational	positive
RNA dependent RNA polymerase	Pancuronium	Computational	positive
RNA dependent RNA polymerase	Dabigatran etexilate	Computational	positive
RNA dependent RNA polymerase	Idarubicin	Computational	positive
RNA dependent RNA polymerase	Valganciclovir	Computational	positive
RNA dependent RNA polymerase	Chlorhexidine	Computational	positive
RNA dependent RNA polymerase	Ceftibuten	Computational	positive
RNA dependent RNA polymerase	Fenoterol	Computational	positive
RNA dependent RNA polymerase	Fludarabine	Computational	positive
RNA dependent RNA polymerase	Cefuroxime	Computational	positive
RNA dependent RNA polymerase	Atovaquone	Computational	positive
RNA dependent RNA polymerase	Tibolone	Computational	positive
RNA dependent RNA polymerase	Bromocriptine	Computational	positive
RNA dependent RNA polymerase	Diphenoxylate	Computational	positive
Helicase	Lymecycline	Computational	positive
Helicase	Cefsulodin	Computational	positive
Helicase	Rolitetracycline	Computational	positive
Helicase	Itraconazole	Computational	positive
Helicase	Dabigatran etexilate	Computational	positive
Helicase	canrenoic acid	Computational	positive
Helicase	Rutin	Computational	positive
Helicase	Saquinavir	Computational	positive
Helicase	Hesperidin	Computational	positive
Angiotensin-converting enzyme 2-Spike glycoprotein interface	Hesperidin	Computational	positive
3C-like protease	Conivaptan	Computational	positive
3C-like protease	Cefpiramide	Computational	positive
3C-like protease	Hesperidin	Computational	positive
RNA dependent RNA polymerase	Itraconazole	Computational	positive
Papain-like proteinases 1/2	Ribavirin	Computational	positive
3C-like protease	Ribavirin	Computational	positive
3C-like protease	Carvedilol	Computational	positive
3C-like protease	Chlorhexidine	Computational	positive
3C-like protease	Lymecycline	Computational	positive
3C-like protease	Oxytetracycline	Computational	positive
3C-like protease	Fosamprenavir	Computational	positive
Papain-like proteinases 1/2	Valganciclovir	Computational	positive
3C-like protease	Telmisartan	Computational	positive
3C-like protease	Montelukast	Computational	positive