ArticlePLoS pathogens2010
Fidelity variants of RNA dependent RNA polymerases uncover an indirect, mutagenic activity of amiloride compounds.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 86 citations in OpenAlex.
- Identification of fidelity-determined residues of Porcine reproductive and respiratory syndrome virus through structural alignment.Virulence · 2026Article
- Mutation in enterovirus 71 nonstructural protein 3A increases genome replication fidelity and exhibits attenuated virulence in mice.Journal of virology · 2025Article
- Mechanism of Forced-Copy-Choice RNA Recombination by Enteroviral RNA-Dependent RNA Polymerases.ACS bio & med chem Au · 2025Article
- The multiple roles of viral 3DVirulence · 2024Review
- Alterations of SARS-CoV-2 Evolutionary Dynamics by Pharmaceutical Factors.Infectious diseases & immunity · 2024Review
- Inter and intra-host diversity of RSV in hematopoietic stem cell transplant adults with normal and delayed viral clearance.Virus evolution · 2024Article
- Mutational analysis of catalytic site domain of CCHFV L RNA segment.Journal of molecular modeling · 2023Article
- Is it time to switch to a formulation other than the live attenuated poliovirus vaccine to prevent poliomyelitis?Frontiers in public health · 2023Review
- RNA-Dependent RNA Polymerase of the Second Human Pegivirus Exhibits a High-Fidelity Feature.Microbiology spectrum · 2022Article
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- Amino Acid Substitutions in NS5 Contribute Differentially to Tembusu Virus Attenuation in Ducklings and Cell Cultures.Viruses · 2021Article
- Porcine Reproductive and Respiratory Syndrome Modified Live Virus Vaccine: A "Leaky" Vaccine with Debatable Efficacy and Safety.Vaccines · 2021Review
- Genome Evolution of Two Genetically Homogeneous Infectious Bursal Disease Virus Strains During PassagesFrontiers in microbiology · 2021Article
- Inhibition of viral RNA-dependent RNA polymerases with clinically relevant nucleotide analogs.The Enzymes · 2021Article
- Polymerase Fidelity Contributes to Foot-and-Mouth Disease Virus Pathogenicity and TransmissibilityJournal of virology · 2020Article
- Within-Host Viral Diversity: A Window into Viral Evolution.Annual review of virology · 2020Review
- Tyr82 Amino Acid Mutation in PB1 Polymerase Induces an Influenza Virus Mutator Phenotype.Journal of virology · 2019Article
- Antiviral effect of amiloride on replication of foot and mouth disease virus in cell culture.Microbial pathogenesis · 2019Article
- Senecavirus-Specific Recombination Assays Reveal the Intimate Link between Polymerase Fidelity and RNA Recombination.Journal of virology · 2019Article
7 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
7 authors at 3 institutions in 2 countries.
Funding
Abstract
In a screen for RNA mutagen resistance, we isolated a high fidelity RNA dependent RNA polymerase (RdRp) variant of Coxsackie virus B3 (CVB3). Curiously, this variant A372V is also resistant to amiloride. We hypothesize that amiloride has a previously undescribed mutagenic activity. Indeed, amiloride compounds increase the mutation frequencies of CVB3 and poliovirus and high fidelity variants of both viruses are more resistant to this effect. We hypothesize that this mutagenic activity is mediated through alterations in intracellular ions such as Mg²+ and Mn²+, which in turn increase virus mutation frequency by affecting RdRp fidelity. Furthermore, we show that another amiloride-resistant RdRp variant, S299T, is completely resistant to this mutagenic activity and unaffected by changes in ion concentrations. We show that RdRp variants resist the mutagenic activity of amiloride via two different mechanisms: 1) increased fidelity that generates virus populations presenting lower basal mutation frequencies or 2) resisting changes in divalent cation concentrations that affect polymerase fidelity. Our results uncover a new antiviral approach based on mutagenesis.
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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.