ArticleJournal of virology2026
Recovery of proofreading-impaired SARS-CoV-2 reveals a mutator phenotype and an ExoN activity threshold for viability.
Li He, Yuan-Wei Norman Su, Fushun Zhang, Ibrahim M Moustafa, David W Gohara, Chengjin Ye, Luis Martinez-Sobrido, Jamie J Arnold, Craig E Cameron, Yan Xiang
Abstract read
In one paragraphArticle in Journal of virology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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1 · What the graph read from itWhat it found
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2 · The registryThe trial behind it
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3 · Its place in the literatureWho cites it
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
10 authors.
Li HeDepartment of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Yuan-Wei Norman SuDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Fushun ZhangDepartment of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Ibrahim M MoustafaThe Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania, USA.
David W GoharaResearch Computing Consultants, LLC, Sanford, Florida, USA.
Jamie J ArnoldDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Craig E CameronDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.ORCID 0000-0002-7564-5642 Yan XiangDepartment of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.ORCID 0000-0002-7633-1629 Funding
Translation Accelerator CoreU19AI171421 · NIAID · STANFORD UNIVERSITY · PI JEFFREY S GLENN · 2022 to 2026
$93.4MTISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Lei Zheng · 1991 to 2026
$59.1MCoronavirus Genome ReplicationR01AI161841 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Jamie Jon Arnold, CRAIG E. CAMERON · 2021 to 2026
$3.4MHigh Throughput DNA Sequencer: Illumina HiSeq 3000 SequencerS10OD021805 · OD · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI LAI, ZHAO · 2016 to 2016
$600kNational Institute of Allergy and Infectious Diseases R01AI161841National Institute of Allergy and Infectious Diseases U19AI171421NCI NIH HHS P30 CA054174NIAID NIH HHS R01 AI161841NIAID NIH HHS U19 AI171421NIH HHS S10 OD021805
6 · The paper itselfAbstract
Coronaviruses (CoVs) replicate unusually large RNA genomes that necessitate proofreading by the 3'-to-5' exoribonuclease (ExoN) formed by nonstructural proteins 14 (nsp14) and 10 (nsp10). Previous studies suggested that inactivation of the ExoN catalytic site in severe acute respiratory syndrome CoV 2 (SARS-CoV-2) is lethal, leaving unresolved whether the virus can tolerate impaired proofreading activity. Here, we investigated the functional requirement for ExoN in SARS-CoV-2 replication by combining a continuous fluorescence-based biochemical assay with an optimized single-bacmid reverse genetics system. Mutational analysis of residues involved in RNA binding or catalysis revealed graded effects on ExoN activity
Indexed as
ExoribonucleasesSARS-CoV-2Viral Nonstructural ProteinsVirus ReplicationAmino Acid SubstitutionAnimalsChlorocebus aethiopsCOVID-19Genome, ViralHumansMutationPhenotypeRNA ReplicationRNA, ViralVero CellsExoribonucleasesRNA, ViralViral Nonstructural Proteinscoronavirus nsp14ExoNgenome stabilitymutator phenotypeproofreadingreplication fidelityreverse geneticsSARS-CoV-2
Identifiers
PMID42524883
PMCPMC13483246
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