Identification of key interactions between SARS-CoV-2 main protease and inhibitor drug candidates.

Scientific Reports
Ryunosuke YoshinoMasakazu Sekijima

Abstract

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 1 μs 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.

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Citations

Dec 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Teresa L AugustinTaufiq Rahman
Dec 22, 2020·Briefings in Bioinformatics·Vaishali P WamanChristine Orengo
Oct 21, 2020·Materials Today : Proceedings·Vivek SrivastavaParatpar Sarkar
Mar 16, 2021·Journal of Biomolecular Structure & Dynamics·Debanjan SenSudhan Debnath
Mar 31, 2021·Journal of Chemical Information and Modeling·Giorgio AmendolaSandro Cosconati
May 22, 2021·Molecular Informatics·Pablo Andrei NogaraJoão Batista Teixeira Rocha
Jan 9, 2021·ACS Infectious Diseases·Mark N Namchuk
Jun 15, 2021·The Journal of Physical Chemistry. B·Shigenori TanakaYuji Mochizuki
Jul 28, 2021·Journal of Chemical Information and Modeling·Manuel A LlanosLuciana Gavernet
Jun 27, 2021·Journal of Molecular Biology·G D NoskeA S Godoy

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Methods Mentioned

BETA
X-ray

Software Mentioned

Phase
Maestro
OPLS3e
PROPKA
Simulation Interactions Diagram

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