Abstract
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.
Keywords: Inhibitors; Main protease; Nirmatrelvir; SARS-CoV-2; Variants.
【저자키워드】 SARS-CoV-2, main protease, inhibitors, Nirmatrelvir, variants., 【초록키워드】 COVID-19, Efficacy, Mutation, Vaccines, B.1.351, COVID-19 pandemic, variant, protease, omicron, inhibitors, variants, Spike protein, Antiviral agents, Effectiveness, drug target, Missense mutation, P.2, Beta, PF-07321332, B.1.1.529, antiviral agent, inhibitor, Nirmatrelvir, Lambda, not compromised, M pro, wildtype, multiple mutations, Coronaviral, Specific, Multiple, public health threat, in vitro data, variants of SARS-CoV-2, SARS-CoV-2 lineage, prevalent, the spike protein, expressed, competent, anticipated, catalytically, 【제목키워드】 SARS-CoV-2 variant, mutant, Nirmatrelvir, susceptible,