ReviewRNA biology
Coronaviruses: an RNA proofreading machine regulates replication fidelity and diversity.
Review in RNA biology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 331 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
331 citing papers in PubMed, 2 syntheses or guidelines pooled it, 518 citations in OpenAlex.
- Potency of BNT162b2 and mRNA-1273 vaccine-induced neutralizing antibodies against severe acute respiratory syndrome-CoV-2 variants of concern: A systematic review of in vitro studies.Reviews in medical virology · 2022Pooled it
- Pooled it
- Transcription Regulatory Sequences in Coronaviruses: Mechanistic Foundations for Antivirals and Vaccines.Journal of microbiology and biotechnology · 2026Review
- Chimeric SARS-CoV-2 vaccine vectors stably incorporating the functional glycoprotein of VSV.iScience · 2026Article
- A bireporter recombinant SARS-CoV-2 Omicron BA.5 forMicrobiology spectrum · 2026Article
- Pathogenicity Difference Between Male and Female mice by Recent SARS-CoV-2/2025.Current microbiology · 2026Article
- Distinct modes of RNA degradation by the structurally related coronavirus and arenavirus exoribonucleases.Journal of virology · 2026Article
- Recovery of proofreading-impaired SARS-CoV-2 reveals a mutator phenotype and an ExoN activity threshold for viability.Journal of virology · 2026Article
- Article
- Article
- Recovery of proofreading-impaired SARS-CoV-2 reveals a mutator phenotype and an ExoN activity threshold for viability.bioRxiv : the preprint server for biology · 2026Article
- SARS-CoV-2 Error Catastrophe Under Molnupiravir: Mutagenic Enhancement Enables Viral Persistence with Impaired Fitness.Viruses · 2026Article
- Suidae Coronaviruses: Epidemiology, Transmission, and Molecular Diagnosis.Animals : an open access journal from MDPI · 2026Review
- SARS-CoV-2 intra-host evolution during acute infection in COVID-19 patients.Frontiers in microbiology · 2026Article
- Antigenic remodeling of the SARS-CoV-2 Spike N-terminal domain links sequence variability to structural reorganization of a neutralizing antibody supersite.Frontiers in cellular and infection microbiology · 2026Article
- Development of RNA Aptamers That Inhibit the RNA-Dependent RNA Polymerase Activity of SARS-CoV-2 Strains In Vitro.International journal of molecular sciences · 2025Article
- Mutation in enterovirus 71 nonstructural protein 3A increases genome replication fidelity and exhibits attenuated virulence in mice.Journal of virology · 2025Article
- Discovery of Galloyl-Flavonoid Conjugates as SARS-CoV-2 3CLInternational journal of molecular sciences · 2025Article
- Rapid Discovery of Potent Neutralizing Antibodies against SARS-CoV-2 through Directed Evolution of SARS-CoV-1 Antibodies.Molecular pharmaceutics · 2025Article
- The mutational landscape of SARS-CoV-2 provides new insight into viral evolution and fitness.Nature communications · 2025Article
271 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
In order to survive and propagate, RNA viruses must achieve a balance between the capacity for adaptation to new environmental conditions or host cells with the need to maintain an intact and replication competent genome. Several virus families in the order Nidovirales, such as the coronaviruses (CoVs) must achieve these objectives with the largest and most complex replicating RNA genomes known, up to 32 kb of positive-sense RNA. The CoVs encode sixteen nonstructural proteins (nsp 1-16) with known or predicted RNA synthesis and modification activities, and it has been proposed that they are also responsible for the evolution of large genomes. The CoVs, including murine hepatitis virus (MHV) and SARS-CoV, encode a 3'-to-5' exoribonuclease activity (ExoN) in nsp14. Genetic inactivation of ExoN activity in engineered SARS-CoV and MHV genomes by alanine substitution at conserved DE-D-D active site residues results in viable mutants that demonstrate 15- to 20-fold increases in mutation rates, up to 18 times greater than those tolerated for fidelity mutants of other RNA viruses. Thus nsp14-ExoN is essential for replication fidelity, and likely serves either as a direct mediator or regulator of a more complex RNA proofreading machine, a process previously unprecedented in RNA virus biology. Elucidation of the mechanisms of nsp14-mediated proofreading will have major implications for our understanding of the evolution of RNA viruses, and also will provide a robust model to investigate the balance between fidelity, diversity and pathogenesis. The discovery of a protein distinct from a viral RdRp that regulates replication fidelity also raises the possibility that RNA genome replication fidelity may be adaptable to differing replication environments and selective pressures, rather than being a fixed determinant.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.