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10.1371/journal.ppat.1009226

http://scihub22266oqcxt.onion/10.1371/journal.ppat.1009226
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33465137!7846108!33465137
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suck abstract from ncbi


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pmid33465137      PLoS+Pathog 2021 ; 17 (1): e1009226
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  • The coronavirus proofreading exoribonuclease mediates extensive viral recombination #MMPMID33465137
  • Gribble J; Stevens LJ; Agostini ML; Anderson-Daniels J; Chappell JD; Lu X; Pruijssers AJ; Routh AL; Denison MR
  • PLoS Pathog 2021[Jan]; 17 (1): e1009226 PMID33465137show ga
  • Recombination is proposed to be critical for coronavirus (CoV) diversity and emergence of SARS-CoV-2 and other zoonotic CoVs. While RNA recombination is required during normal CoV replication, the mechanisms and determinants of CoV recombination are not known. CoVs encode an RNA proofreading exoribonuclease (nsp14-ExoN) that is distinct from the CoV polymerase and is responsible for high-fidelity RNA synthesis, resistance to nucleoside analogues, immune evasion, and virulence. Here, we demonstrate that CoVs, including SARS-CoV-2, MERS-CoV, and the model CoV murine hepatitis virus (MHV), generate extensive and diverse recombination products during replication in culture. We show that the MHV nsp14-ExoN is required for native recombination, and that inactivation of ExoN results in decreased recombination frequency and altered recombination products. These results add yet another critical function to nsp14-ExoN, highlight the uniqueness of the evolved coronavirus replicase, and further emphasize nsp14-ExoN as a central, completely conserved, and vulnerable target for inhibitors and attenuation of SARS-CoV-2 and future emerging zoonotic CoVs.
  • |*COVID-19 Drug Treatment[MESH]
  • |Antiviral Agents/pharmacology[MESH]
  • |COVID-19/virology[MESH]
  • |Coronavirus Infections/*drug therapy/virology[MESH]
  • |Exoribonucleases/genetics/*pharmacology[MESH]
  • |Humans[MESH]
  • |Recombination, Genetic/drug effects[MESH]
  • |SARS-CoV-2/*drug effects/pathogenicity[MESH]
  • |Viral Nonstructural Proteins/genetics[MESH]


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