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SARS-Mpro-MD-Rxiv-manuscript.pdf (642.94 kB)

Identification of Key Interactions Between SARS-CoV-2 Main Protease and Inhibitor Drug Candidates

submitted on 20.03.2020, 04:10 and posted on 23.03.2020, 12:27 by Ryunosuke Yoshino, Nobuaki Yasuo, Masakazu Sekijima

The number of cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) has reached over 114,000. SARS-CoV-2 caused a pandemic in Wuhan, China, in December 2019 and is rapidly spreading globally. It has been reported that peptide-like anti-HIV-1 drugs are effective against SARS-CoV Main protease (Mpro). Due to the close phylogenetic relationship between SARS-CoV and SARS-CoV-2, their main proteases share many structural and functional features. Thus, these drugs are also regarded as potential drug candidates targeting SARS-CoV-2 Mpro. However, the mechanism of action of SARS-CoV-2 Mpro at the atomic-level is unknown. In the present study, we revealed key interactions between SARS-CoV-2 Mpro and three drug candidates by performing pharmacophore modeling and 1μs molecular dynamics (MD) simulations. His41, Gly143, and Glu166 formed interactions with the functional groups that were common among peptide-like inhibitors in all MD simulations. These interactions are important targets for potential drugs against SARS-CoV-2 Mpro.


the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED under Grant Number JP19am0101112j0003


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Tokyo Institute of technology



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Declaration of Conflict of Interest

The authors declare no competing interests.