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

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

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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 antiviral 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.

SARS-CoV-2Drug repurposingMolecular dockingRemdesivirHomology modeling

Canrong Wu、Yang Liu、Yueying Yang、Peng Zhang、Wu Zhong、Yali Wang、Qiqi Wang、Yang Xu、Mingxue Li、Xingzhou Li、Mengzhu Zheng、Lixia Chen、Hua Li

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Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education,Shenyang Pharmaceutical University, Shenyang 110016, China

National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

We acknowledge support from National Mega-project for Innovative DrugsWe acknowledge support from National Mega-project for Innovative DrugsNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of Chinaand the Fundamental Research Fund

grant number 2019ZX09721001-004-007ChinaNSFCgrant numbers U18031228177363781773594U1703111

2020

药学学报(英文版)

药学学报(英文版)

CSTPCDCSCDSCI
ISSN：
年,卷(期)：2020.10(5)
  • 43
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