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

preprint
submitted on 20.03.2020 and posted on 23.03.2020 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.

Funding

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

History

Email Address of Submitting Author

sekijima@c.titech.ac.jp

Institution

Tokyo Institute of technology

Country

Japan

ORCID For Submitting Author

0000-0002-3806-9535

Declaration of Conflict of Interest

The authors declare no competing interests.

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