Open AccessPotential anti‐SARS‐CoV‐2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease
Author(s) -
Tsuji Motonori
Publication year - 2020
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12875
Subject(s) - chembl , protease , virtual screening , coronavirus , protein data bank (rcsb pdb) , docking (animal) , peptidomimetic , drug repositioning , covid-19 , drug discovery , chemistry , drug , antiviral drug , computational biology , pharmacology , virology , biology , medicine , biochemistry , enzyme , infectious disease (medical specialty) , disease , pathology , peptide , nursing
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 pro , also called 3‐chymotrypsin‐like protease) of SARS‐CoV‐2 is a potential target for treatment of COVID‐19. A M pro 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 pro 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 pro . Additional docking simulations for predicted compounds with high binding affinity with M pro 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.