Potential anti‐SARS‐CoV‐2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease

摘要

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 (Msuppro/sup, also called 3‐chymotrypsin‐like protease) of SARS‐CoV‐2 is a potential target for treatment of COVID‐19. A Msuppro/sup homodimer structure suitable for docking simulations was prepared using a crystal structure (PDB ID: 6Y2G ; resolution 2.20??). Structural refinement was performed in the presence of peptidomimetic α‐ketoamide inhibitors, which were previously disconnected from each Cys145 of the Msuppro/sup 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 Msuppro/sup. Additional docking simulations for predicted compounds with high binding affinity with Msuppro/sup 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.