ArticlemBio2017
Proofreading-Deficient Coronaviruses Adapt for Increased Fitness over Long-Term Passage without Reversion of Exoribonuclease-Inactivating Mutations.
Article in mBio, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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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.
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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.
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Who cites it
48 citing papers in PubMed, 76 citations in OpenAlex.
- Recovery of proofreading-impaired SARS-CoV-2 reveals a mutator phenotype and an ExoN activity threshold for viability.Journal of virology · 2026Article
- Concepts of RNA virus evolution for the design of better antiviral countermeasures.Nature reviews. Microbiology · 2026Review
- Narrowed host ranges do not constrain future host range expansion in RNA phage Φ6.Journal of virology · 2026Article
- 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
- Article
- SARS-CoV-2 Remdesivir Exposure Leads to Different Evolutionary Pathways That Converge in Moderate Levels of Drug Resistance.Viruses · 2025Article
- Long-term serial passaging of SARS-CoV-2 reveals signatures of convergent evolution.Journal of virology · 2025Article
- The coronavirus nsp14 exoribonuclease interface with the cofactor nsp10 is essential for efficient virus replication and enzymatic activity.Journal of virology · 2025Article
- Dynamic Combinatorial Chemistry Unveils Nsp10 Inhibitors with Antiviral Potential Against SARS-CoV-2.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Biochemical simulation of mutation synthesis and repair during SARS-CoV-2 RNA polymerization.Virology · 2024Article
- A Proofreading Mutation with an Allosteric Effect Allows a Cluster of SARS-CoV-2 Viruses to Rapidly Evolve.Molecular biology and evolution · 2023Article
- SARS-CoV-2 entry into and evolution within a skilled nursing facility.Scientific reports · 2023Article
- How hydrolytic exoribonucleases impact human disease: Two sides of the same story.FEBS open bio · 2023Review
- CRISPR techniques and potential for the detection and discrimination of SARS-CoV-2 variants of concern.Trends in analytical chemistry : TRAC · 2023Review
- Article
- COVID-19: A state of art on immunological responses, mutations, and treatment modalities in riposte.Journal of infection and public health · 2023Review
- Cellular APOBEC3A deaminase drives mutations in the SARS-CoV-2 genome.Nucleic acids research · 2023Article
- Virus Diversity, Abundance, and Evolution in Three Different Bat Colonies in Switzerland.Viruses · 2022Article
- Proteolytic Processing of the Coronavirus Replicase Nonstructural Protein 14 Exonuclease Is Not Required for Virus Replication but Alters RNA Synthesis and Viral Fitness.Journal of virology · 2022Article
- Mutations in the SARS-CoV-2 RNA-dependent RNA polymerase confer resistance to remdesivir by distinct mechanisms.Science translational medicine · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The coronavirus (CoV) RNA genome is the largest among the single-stranded positive-sense RNA viruses. CoVs encode a proofreading 3'-to-5' exoribonuclease within nonstructural protein 14 (nsp14-ExoN) that is responsible for CoV high-fidelity replication. Alanine substitution of ExoN catalytic residues [ExoN(-)] in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and murine hepatitis virus (MHV) disrupts ExoN activity, yielding viable mutant viruses with defective replication, up to 20-fold-decreased fidelity, and increased susceptibility to nucleoside analogues. To test the stability of the ExoN(-) genotype and phenotype, we passaged MHV-ExoN(-) 250 times in cultured cells (P250), in parallel with wild-type MHV (WT-MHV). Compared to MHV-ExoN(-) P3, MHV-ExoN(-) P250 demonstrated enhanced replication and increased competitive fitness without reversion at the ExoN(-) active site. Furthermore, MHV-ExoN(-) P250 was less susceptible than MHV-ExoN(-) P3 to multiple nucleoside analogues, suggesting that MHV-ExoN(-) was under selection for increased replication fidelity. We subsequently identified novel amino acid changes within the RNA-dependent RNA polymerase and nsp14 of MHV-ExoN(-) P250 that partially accounted for the reduced susceptibility to nucleoside analogues. Our results suggest that increased replication fidelity is selected in ExoN(-) CoVs and that there may be a significant barrier to ExoN(-) reversion. These results also support the hypothesis that high-fidelity replication is linked to CoV fitness and indicate that multiple replicase proteins could compensate for ExoN functions during replication.
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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.