Biochemical simulation of mutation synthesis and repair during SARS-CoV-2 RNA polymerization.

Autor: Oo A; Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, 30322, USA., Chen Z; Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, 30329, USA., Cao D; Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, 30329, USA., Cho YJ; Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, 30322, USA., Liang B; Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, 30329, USA., Schinazi RF; Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, 30322, USA; Center for ViroScience and Cure, Children's Healthcare of Atlanta, GA, 30322, USA., Kim B; Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, 30322, USA; Center for ViroScience and Cure, Children's Healthcare of Atlanta, GA, 30322, USA. Electronic address: baek.kim@emory.edu.
Jazyk: angličtina
Zdroj: Virology [Virology] 2024 Dec; Vol. 600, pp. 110255. Date of Electronic Publication: 2024 Oct 01.
DOI: 10.1016/j.virol.2024.110255
Abstrakt: We biochemically simulated the mutation synthesis process of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) complex (nsp7/nsp8/nsp12) involving two sequential mechanistic steps that occur during genomic replication: misinsertion (incorporation of incorrect nucleotides) and mismatch extension. Then, we also simulated mismatch repair process catalyzed by the viral nsp10/nsp14 ExoN complex. In these mechanistic simulations, while SARS-CoV-2 RdRp displays efficient mutation synthesis capability, the viral ExoN complex was able to effectively repair the mismatch primers generated during the mutation synthesis. Also, we observed that the delayed RNA synthesis induced by mutation synthesis process was rescued by the viral ExoN activity. Collectively, our biochemical simulations suggest that SARS-CoV-2 ExoN complex may contribute to both maintenance of proper viral genetic diversity levels and successful completion of the viral large RNA genome replication by removing mismatches generated by the viral RdRp.
Competing Interests: Declaration of competing interest 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.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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