Is PF-00835231 a Pan-SARS-CoV-2 Mpro Inhibitor? A Comparative Study

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Authors: Mohammad Hassan Baig ; Tanuj Sharma ; Irfan Ahmad ; Mohammed Abohashrh ; Mohammad Mahtab Alam ; Jae-June Dong

MeSH: Antiviral Agents / chemistry* ; Antiviral Agents / pharmacology* ; Binding Sites ; COVID-19 / drug therapy ; Computer Simulation ; Coronavirus 3C Proteases / antagonists & inhibitors* ; Coronavirus 3C Proteases / chemistry ; Coronavirus 3C Proteases / genetics ; Databases, Protein ; Diarylquinolines / chemistry ; Diarylquinolines / pharmacology ; Dihydropyridines / chemistry ; Dihydropyridines / pharmacology ; Humans ; Indoles / chemistry* ; Indoles / pharmacology* ; Leucine / chemistry* ; Leucine / pharmacology* ; Ligands ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Nitrobenzenes / chemistry ; Nitrobenzenes / pharmacology ; Nitrophenols / chemistry ; Nitrophenols / pharmacology ; Organophosphorus Compounds / chemistry ; Organophosphorus Compounds / pharmacology ; Piperazines / chemistry ; Piperazines / pharmacology ; Proline / analogs & derivatives ; Proline / chemistry ; Proline / pharmacology ; Protease Inhibitors / chemistry* ; Protease Inhibitors / pharmacology* ; Pyrrolidinones / chemistry* ; Pyrrolidinones / pharmacology* ; SARS-CoV-2 / drug effects ; SARS-CoV-2 / genetics

Abstract: The COVID-19 outbreak continues to spread worldwide at a rapid rate. Currently, the absence of any effective antiviral treatment is the major concern for the global population. The reports of the occurrence of various point mutations within the important therapeutic target protein of SARS-CoV-2 has elevated the problem. The SARS-CoV-2 main protease (Mpro) is a major therapeutic target for new antiviral designs. In this study, the efficacy of PF-00835231 was investigated (a Mpro inhibitor under clinical trials) against the Mpro and their reported mutants. Various in silico approaches were used to investigate and compare the efficacy of PF-00835231 and five drugs previously documented to inhibit the Mpro. Our study shows that PF-00835231 is not only effective against the wild type but demonstrates a high affinity against the studied mutants as well.