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A proofreading mutation with an allosteric effect allows a cluster of SARS-CoV-2 viruses to rapidly evolve

Mack, Andrew H., Menzies, Georgina ORCID:, Southgate, Alex, Jones, D. Dafydd ORCID:, Connor, Thomas R. ORCID: and Leitner, Thomas 2023. A proofreading mutation with an allosteric effect allows a cluster of SARS-CoV-2 viruses to rapidly evolve. Molecular Biology and Evolution 40 (10) , msad209. 10.1093/molbev/msad209

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The RNA-dependent RNA polymerase of the severe acute respiratory syndrome coronavirus 2 virus is error prone, with errors being corrected by the exonuclease (NSP14) proofreading mechanism. However, the mutagenesis and subsequent evolutionary trajectory of the virus is mediated by the delicate interplay of replicase fidelity and environmental pressures. Here, we have shown that a single, distal mutation (F60S) in NSP14 can have a profound impact upon proofreading with an increased accumulation of mutations and elevated evolutionary rate being observed. Understanding the implications of these changes is crucial, as these underlying mutational processes may have important implications for understanding the population-wide evolution of the virus. This study underscores the urgent need for continued research into the replicative mechanisms of this virus to combat its continued impact on global health, through the re-emergence of immuno-evasive variants.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Advanced Research Computing @ Cardiff (ARCCA)
Publisher: Oxford University Press
ISSN: 0737-4038
Date of First Compliant Deposit: 6 October 2023
Date of Acceptance: 20 September 2023
Last Modified: 07 Jun 2024 16:19

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