Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir

被引：127

作者：

Ullrich, Sven ^{[1
]}

Ekanayake, Kasuni B. ^{[1
]}

Otting, Gottfried ^{[1
]}

Nitsche, Christoph ^{[1
]}

机构：

[1] Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2022年 / 62卷

基金：

澳大利亚研究理事会;

关键词：

SARS-CoV-2; Main protease; Variants; Nirmatrelvir; Inhibitors; CORONAVIRUS 3C-LIKE PROTEASE; DIMER INTERFACE; SARS; DIMERIZATION; CATALYSIS; MUTATIONS; VACCINES;

D O I：

10.1016/j.bmcl.2022.128629

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The COVID-19 pandemic continues to be a public health threat. Multiple mutations in the spike protein of emerging variants of SARS-CoV-2 appear to impact on the effectiveness of available vaccines. Specific antiviral agents are keenly anticipated but their efficacy may also be compromised in emerging variants. One of the most attractive coronaviral drug targets is the main protease (M-pro). A promising M-pro inhibitor of clinical relevance is the peptidomimetic nirmatrelvir (PF-07321332). We expressed M-pro of six SARS-CoV-2 lineages (C.37 Lambda, B.1.1.318, B.1.2, B.1.351 Beta, B.1.1.529 Omicron, P.2 Zeta), each of which carries a strongly prevalent missense mutation (G15S, T21I, L89F, K90R, P132H, L205V). Enzyme kinetics reveal that these M-pro variants are catalytically competent to a similar degree as the wildtype. We show that nirmatrelvir has similar potency against the variants as the wildtype. Our in vitro data suggest that the efficacy of the specific M-pro inhibitor nirmatrelvir is not compromised in current COVID-19 variants.

引用

页数：4

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