Computational Determination of Potential Inhibitors of SARS-CoV-2 Main Protease.

Journal of Chemical Information and Modeling
Son Tung NgoVan V Vu

Abstract

The novel coronavirus (SARS-CoV-2) has infected several million people and caused thousands of deaths worldwide since December 2019. As the disease is spreading rapidly all over the world, it is urgent to find effective drugs to treat the virus. The main protease (Mpro) of SARS-CoV-2 is one of the potential drug targets. Therefore, in this context, we used rigorous computational methods, including molecular docking, fast pulling of ligand (FPL), and free energy perturbation (FEP), to investigate potential inhibitors of SARS-CoV-2 Mpro. We first tested our approach with three reported inhibitors of SARS-CoV-2 Mpro, and our computational results are in good agreement with the respective experimental data. Subsequently, we applied our approach on a database of ∼4600 natural compounds, as well as 8 available HIV-1 protease (PR) inhibitors and an aza-peptide epoxide. Molecular docking resulted in a short list of 35 natural compounds, which was subsequently refined using the FPL scheme. FPL simulations resulted in five potential inhibitors, including three natural compounds and two available HIV-1 PR inhibitors. Finally, FEP, the most accurate and precise method, was used to determine the absolute binding free energy of these five co...Continue Reading

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Citations

Sep 6, 2020·Pharmacological Reports : PR·Thakur Uttam SinghRaj Kumar Singh
Dec 20, 2020·Journal of Molecular Graphics & Modelling·Son Tung NgoHuong Thi Thu Phung
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Apr 9, 2021·Journal of Chemical Information and Modeling·Son Tung NgoTrung Hai Nguyen
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Oct 31, 2021·Journal of Computational Chemistry·T Ngoc Han PhamSon Tung Ngo

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Software Mentioned

PreADME
ACPYPE
PyMOL
AmberTools18
AutodockTools
FPL
LigPlot + +
CADD
Autodock Vina
GROMACS

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