Main protease mutants of SARS-CoV-2 variants remain susceptible to PF-07321332

Ullrich et al., bioRxiv, doi:10.1101/2021.11.28.4702264

Nov 2021

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In Vitro study showing that PF-07321332 maintains efficacy against variants C.37 lambda, B.1.1.318, B.1.2, B.1.351 beta, and P.2 zeta.

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Ullrich et al., 30 Nov 2021, preprint, 4 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

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Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir (PF-07321332)

Sven Ullrich, Kasuni B Ekanayake, Gottfried Otting, Christoph Nitsche

doi:10.1101/2021.11.28.470226

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 PF-07321332. We expressed M pro 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 M pro 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 M pro inhibitors such as PF-07321332 is not compromised in current COVID-19 variants. .

Competing Interest Declaration The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Author Information Sven Ullrich, ORCID: 0000-0003-4184-7024 Kasuni B. Ekanayake, ORCID: 0000-0002-3078-5895 Gottfried Otting, ORCID: 0000-0002-0563-0146 Christoph Nitsche, ORCID: 0000-0002-3704-2699

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