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Comparative Study
. 2021 Mar 17;26(6):1678.
doi: 10.3390/molecules26061678.

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

Mohammad Hassan Baig  1 , Tanuj Sharma  1 , Irfan Ahmad  2 , Mohammed Abohashrh  3 , Mohammad Mahtab Alam  3 , Jae-June Dong  1
Affiliations
Comparative Study

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

Mohammad Hassan Baig et al. Molecules. .

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.

Keywords: PF-00835231; SARS-CoV-2; inhibitors; main protease; mutants.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of all of the compounds investigated in this study. (a) PF-00835231; (b) Boceprevir; (c) Manidipine; (d) Efonidipine; (e) Lercanidipine; (f) Bedaquiline.
Figure 2
Figure 2
The selected mutant investigated in this study.
Figure 3
Figure 3
Complex of PF-00835231 within the active site of (a) WT; (b) Y54C.
Figure 4
Figure 4
Complex of Efonidipine within the active site of (a) N142S; (b) T190I.
Figure 5
Figure 5
Molecular dynamics results of the PF-07304814 and Efonidipine bound complexes of the WT Mpro (black), Y54C (yellow), N142S (green), T190I (blue) and A1901V (red). The backbone RMSD of the Mpro (WT) and mutants in complex with (a) PF-07304814; (b) Efonidipine. The ligand RMSD of (c) PF-07304814 and (d) Efonidipine during the 100 ns. The intermolecular hydrogen bond formations of the (e) PF-07304814 and (f) Efonidipine bound complex.
See this image and copyright information in PMC

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