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Editor, Senior Moderator
FEBS Open Bio. 2020 May 6. doi: 10.1002/2211-5463.12875. [Epub ahead of print]
Potential anti-SARS-CoV-2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease.
Tsuji M[SUP]1[/SUP].
Author information
Abstract
A novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], or 2019 novel coronavirus [2019-nCoV]) has been identified as the pathogen of coronavirus disease 2019 (COVID-19). The main protease (M[SUP]pro[/SUP] , also called 3-chymotrypsin-like protease [3CL[SUP]pro[/SUP] ]) of SARS-CoV-2 is a potential target for treatment of COVID-19. A M[SUP]pro[/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 M[SUP]pro[/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 M[SUP]pro[/SUP] . Additional docking simulations for predicted compounds with high binding affinity with M[SUP]pro[/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.
This article is protected by copyright. All rights reserved.
KEYWORDS:
2019-nCoV; COVID-19; Drug Repositioning; Mpro; SARS-CoV-2; Virtual Screening
PMID:32374074DOI:10.1002/2211-5463.12875
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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.
Tsuji M[SUP]1[/SUP].
Author information
Abstract
A novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], or 2019 novel coronavirus [2019-nCoV]) has been identified as the pathogen of coronavirus disease 2019 (COVID-19). The main protease (M[SUP]pro[/SUP] , also called 3-chymotrypsin-like protease [3CL[SUP]pro[/SUP] ]) of SARS-CoV-2 is a potential target for treatment of COVID-19. A M[SUP]pro[/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 M[SUP]pro[/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 M[SUP]pro[/SUP] . Additional docking simulations for predicted compounds with high binding affinity with M[SUP]pro[/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.
This article is protected by copyright. All rights reserved.
KEYWORDS:
2019-nCoV; COVID-19; Drug Repositioning; Mpro; SARS-CoV-2; Virtual Screening
PMID:32374074DOI:10.1002/2211-5463.12875
Free full text