RT Journal Article SR Electronic T1 Main protease mutants of SARS-CoV-2 variants remain susceptible to PF-07321332 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.11.28.470226 DO 10.1101/2021.11.28.470226 A1 Sven Ullrich A1 Kasuni B. Ekanayake A1 Gottfried Otting A1 Christoph Nitsche YR 2021 UL http://biorxiv.org/content/early/2021/11/30/2021.11.28.470226.abstract AB 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 (Mpro). A promising Mpro inhibitor of clinical relevance is the peptidomimetic PF-07321332. We expressed Mpro of five SARS-CoV-2 lineages (C.37 Lambda, B.1.1.318, B.1.2, B.1.351 Beta, P.2 Zeta), each of which carries a strongly prevalent missense mutation (G15S, T21I, L89F, K90R, L205V). Enzyme kinetics showed that these Mpro variants are similarly catalytically competent as the wildtype. We show that PF-07321332 has similar potency against the variants as against the wildtype. Our in vitro data suggest that the efficacy of specific Mpro inhibitors such as PF-07321332 is not compromised in current COVID-19 variants.Competing Interest StatementThe authors have declared no competing interest.