Theoretical Analysis Reveals the Cost and Benefit of Proofreading in Coronavirus Genome Replication

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dc.citation.firstpage2691
dc.citation.issueNumber10
dc.citation.journalTitleThe Journal of Physical Chemistry Letters
dc.citation.lastpage2698
dc.citation.volumeNumber12
dc.contributor.authorMallory, Joel D.
dc.contributor.authorMallory, Xian F.
dc.contributor.authorKolomeisky, Anatoly B.
dc.contributor.authorIgoshin, Oleg A.
dc.contributor.orgCenter for Theoretical Biological Physics
dc.date.accessioned2021-05-05T19:51:23Z
dc.date.available2021-05-05T19:51:23Z
dc.date.issued2021
dc.description.abstractSevere acute respiratory syndrome coronaviruses have unusually large RNA genomes replicated by a multiprotein complex containing an RNA-dependent RNA polymerase (RdRp). Exonuclease activity enables the RdRp complex to remove wrongly incorporated bases via proofreading, a process not utilized by other RNA viruses. However, it is unclear why the RdRp complex needs proofreading and what the associated trade-offs are. Here we investigate the interplay among the accuracy, speed, and energetic cost of proofreading in the RdRp complex using a kinetic model and bioinformatics analysis. We find that proofreading nearly optimizes the rate of functional virus production. However, we find that further optimization would lead to a significant increase in the proofreading cost. Unexpected importance of the cost minimization is further supported by other global analyses. We speculate that cost optimization could help avoid cell defense responses. Thus, proofreading is essential for the production of functional viruses, but its rate is limited by energy costs.
dc.identifier.citationMallory, Joel D., Mallory, Xian F., Kolomeisky, Anatoly B., et al.. "Theoretical Analysis Reveals the Cost and Benefit of Proofreading in Coronavirus Genome Replication." <i>The Journal of Physical Chemistry Letters,</i> 12, no. 10 (2021) American Chemical Society: 2691-2698. https://doi.org/10.1021/acs.jpclett.1c00190.
dc.identifier.doihttps://doi.org/10.1021/acs.jpclett.1c00190
dc.identifier.urihttps://hdl.handle.net/1911/110482
dc.language.isoeng
dc.publisherAmerican Chemical Society
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Chemical Society.
dc.titleTheoretical Analysis Reveals the Cost and Benefit of Proofreading in Coronavirus Genome Replication
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpost-print
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