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Potential anti-SARS-CoV-2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease.
- Source :
-
FEBS open bio [FEBS Open Bio] 2020 Jun; Vol. 10 (6), pp. 995-1004. Date of Electronic Publication: 2020 May 29. - Publication Year :
- 2020
-
Abstract
- A novel coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or 2019 novel coronavirus] has been identified as the pathogen of coronavirus disease 2019. The main protease (M <superscript>pro</superscript> , also called 3-chymotrypsin-like protease) of SARS-CoV-2 is a potential target for treatment of COVID-19. A M <superscript>pro</superscript> homodimer structure suitable for docking simulations was prepared using a crystal structure (PDB ID: 6Y2G; resolution 2.20 Å). Structural refinement was performed in the presence of peptidomimetic α-ketoamide inhibitors, which were previously disconnected from each Cys145 of the M <superscript>pro</superscript> homodimer, and energy calculations were performed. Structure-based virtual screenings were performed using the ChEMBL database. Through a total of 1 485 144 screenings, 64 potential drugs (11 approved, 14 clinical, and 39 preclinical drugs) were predicted to show high binding affinity with M <superscript>pro</superscript> . Additional docking simulations for predicted compounds with high binding affinity with M <superscript>pro</superscript> suggested that 28 bioactive compounds may have potential as effective anti-SARS-CoV-2 drug candidates. The procedure used in this study is a possible strategy for discovering anti-SARS-CoV-2 drugs from drug libraries that may significantly shorten the clinical development period with regard to drug repositioning.<br /> (© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)
- Subjects :
- Betacoronavirus drug effects
COVID-19
Catalytic Domain
Chymases antagonists & inhibitors
Chymases chemistry
Coronavirus Infections drug therapy
Coronavirus Infections virology
Crystallization
Databases, Chemical
Humans
Models, Molecular
Molecular Docking Simulation
Pandemics
Pharmaceutical Preparations chemistry
Pneumonia, Viral drug therapy
Pneumonia, Viral virology
SARS-CoV-2
Serine Proteinase Inhibitors chemistry
Viral Proteins chemistry
Betacoronavirus enzymology
Chymases metabolism
Coronavirus Infections metabolism
Drug Discovery methods
Drug Repositioning methods
Pharmaceutical Preparations metabolism
Pneumonia, Viral metabolism
Serine Proteinase Inhibitors metabolism
Viral Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-5463
- Volume :
- 10
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- FEBS open bio
- Publication Type :
- Academic Journal
- Accession number :
- 32374074
- Full Text :
- https://doi.org/10.1002/2211-5463.12875