Structure-Based Virtual Screening to Discover Potential Lead Molecules for the SARS-CoV-2 Main Protease

Journal of Chemical Information and Modeling
Anuj GahlawatPrabha Garg

Abstract

The COVID-19 disease is caused by a new strain of the coronavirus family (SARS-CoV-2), and it has affected at present millions of people all over the world. The indispensable role of the main protease (Mpro) in viral replication and gene expression makes this enzyme an attractive drug target. Therefore, inhibition of SARS-CoV-2 Mpro as a proposition to halt virus ingression is being pursued by scientists globally. Here we carried out a study with two objectives: the first being to perform comparative protein sequence and 3D structural analysis to understand the effect of 12 point mutations on the active site. Among these, two mutations, viz., Ser46 and Phe134, were found to cause a significant change at the active sites of SARS-CoV-2. The Ser46 mutation present at the entrance of the S5 subpocket of SARS-CoV-2 increases the contribution of other two hydrophilic residues, while the Phe134 mutation, present in the catalytic cysteine loop, can cause an increase in catalytic efficiency of Mpro by facilitating fast proton transfer from the Cys145 to His41 residue. It was observed that active site remained conserved among Mpro of both SARS-CoVs, except at the entrance of the S5 subpocket, suggesting sustenance of substrate specificit...Continue Reading

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Dec 22, 2020·Briefings in Bioinformatics·Vaishali P WamanChristine Orengo
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Software Mentioned

mCSM
DUET
HTVS
Schrödinger
CASTp tool
thermal
Maestro visualizer
MEGA X
Epik
mmgbsa

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