Inhibitory efficacy and structural insights of Bofutrelvir against SARS-CoV-2 Mpro mutants and MERS-CoV Mpro DOI Creative Commons
Weiwei Wang, Xuelan Zhou, Wen Li

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 25, 2025

The COVID-19 pandemic has caused significant global health and economic disruption. Mutations E166N, E166R, S144A His163A in the SARS-CoV-2 main protease (Mpro) have been implicated reducing efficacy of certain antiviral treatments. Bofutrelvir, a promising inhibitor, shown effectiveness against Mpro. This study aims to evaluate inhibitory effects Bofutrelvir on His163A, E166V mutants Mpro, as well MERS-CoV Our findings indicate substantial reduction potency these MERS-CoV, with IC50 values significantly higher than those for wild-type Specifically, E166V, S144A, H163A mutations reduce binding affinity due disrupted hydrogen bonds, altered site stability, reduced enzyme activity. Structural analysis crystal complexes showed that changes interactions at S1 subsite loss bonds S4 Mpro are critical factors contributing diminished These insights reveal necessity ongoing structural adapt therapeutic strategies. (E166N/R/V, H163A) by disrupting destabilizing pockets, altering enzymatic

Language: Английский

Inhibitory efficacy and structural insights of Bofutrelvir against SARS-CoV-2 Mpro mutants and MERS-CoV Mpro DOI Creative Commons
Weiwei Wang, Xuelan Zhou, Wen Li

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 25, 2025

The COVID-19 pandemic has caused significant global health and economic disruption. Mutations E166N, E166R, S144A His163A in the SARS-CoV-2 main protease (Mpro) have been implicated reducing efficacy of certain antiviral treatments. Bofutrelvir, a promising inhibitor, shown effectiveness against Mpro. This study aims to evaluate inhibitory effects Bofutrelvir on His163A, E166V mutants Mpro, as well MERS-CoV Our findings indicate substantial reduction potency these MERS-CoV, with IC50 values significantly higher than those for wild-type Specifically, E166V, S144A, H163A mutations reduce binding affinity due disrupted hydrogen bonds, altered site stability, reduced enzyme activity. Structural analysis crystal complexes showed that changes interactions at S1 subsite loss bonds S4 Mpro are critical factors contributing diminished These insights reveal necessity ongoing structural adapt therapeutic strategies. (E166N/R/V, H163A) by disrupting destabilizing pockets, altering enzymatic

Language: Английский

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