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10.1021/acs.jpclett.1c00190

http://scihub22266oqcxt.onion/10.1021/acs.jpclett.1c00190
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33689357!ä!33689357

suck abstract from ncbi


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pmid33689357      J+Phys+Chem+Lett 2021 ; 12 (10): 2691-2698
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  • Theoretical Analysis Reveals the Cost and Benefit of Proofreading in Coronavirus Genome Replication #MMPMID33689357
  • Mallory JD; Mallory XF; Kolomeisky AB; Igoshin OA
  • J Phys Chem Lett 2021[Mar]; 12 (10): 2691-2698 PMID33689357show ga
  • Severe 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.
  • |*Models, Theoretical[MESH]
  • |Coronavirus/*genetics/metabolism[MESH]
  • |Kinetics[MESH]
  • |RNA-Dependent RNA Polymerase/*metabolism[MESH]
  • |Viral Proteins/*metabolism[MESH]


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