ArticleNucleic acids research2014
Inhibition of RNA binding to hepatitis C virus RNA-dependent RNA polymerase: a new mechanism for antiviral intervention.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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.
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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Chinese herbal medicine: Fighting SARS-CoV-2 infection on all fronts.Journal of ethnopharmacology · 2021Pooled it
- Advances regarding physiological functions and mechanisms of theaflavin‑3,3'‑digallate (Review).Molecular medicine reports · 2026Review
- Novel Cocrystal of Quercetagetin: In vitro and in vivo Insights into Biopharmaceutical Performance.Pharmaceutical research · 2026Article
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- Exploring the phytochemicals ofJournal of King Saud University. Science · 2022Article
- Quorum sensing modulation and inhibition in biofilm forming foot ulcer pathogens by selected medicinal plants.Heliyon · 2022Article
- In silico and in vitro evaluation of silibinin: a promising anti-Chikungunya agent.In vitro cellular & developmental biology. Animal · 2022Article
- Exploring the Targets of Novel Corona Virus and Docking-based Screening of Potential Natural Inhibitors to Combat COVID-19.Current topics in medicinal chemistry · 2022Article
- Nanotechnology Applications of Flavonoids for Viral Diseases.Pharmaceutics · 2021Review
- Targeting the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge.Molecules (Basel, Switzerland) · 2020Review
- Antiviral Properties of Flavonoids and Delivery Strategies.Nutrients · 2020Review
- Prediction of Small Molecule Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus-2 RNA-dependent RNA Polymerase.ACS omega · 2020Article
- Article
- A screen for novel hepatitis C virus RdRp inhibitor identifies a broad-spectrum antiviral compound.Scientific reports · 2017Article
- In Vitro Study on Anti-Hepatitis C Virus Activity of Spatholobus suberectus Dunn.Molecules (Basel, Switzerland) · 2016Article
- Live Cell Reporter Systems for Positive-Sense Single Strand RNA Viruses.Applied biochemistry and biotechnology · 2016Review
- Fluorometric RdRp assay with self-priming RNA.Virus genes · 2015Article
- Discovery of Metal Ions Chelator Quercetin Derivatives with Potent Anti-HCV Activities.Molecules (Basel, Switzerland) · 2015Article
- Apigenin restricts FMDV infection and inhibits viral IRES driven translational activity.Viruses · 2015Article
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 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) is a key target for antiviral intervention. The goal of this study was to identify the binding site and unravel the molecular mechanism by which natural flavonoids efficiently inhibit HCV RdRp. Screening identified the flavonol quercetagetin as the most potent inhibitor of HCV RdRp activity. Quercetagetin was found to inhibit RdRp through inhibition of RNA binding to the viral polymerase, a yet unknown antiviral mechanism. X-ray crystallographic structure analysis of the RdRp-quercetagetin complex identified quercetagetin's binding site at the entrance of the RNA template tunnel, confirming its original mode of action. This antiviral mechanism was associated with a high barrier to resistance in both site-directed mutagenesis and long-term selection experiments. In conclusion, we identified a new mechanism for non-nucleoside inhibition of HCV RdRp through inhibition of RNA binding to the enzyme, a mechanism associated with broad genotypic activity and a high barrier to resistance. Our results open the way to new antiviral approaches for HCV and other viruses that use an RdRp based on RNA binding inhibition, that could prove to be useful in human, animal or plant viral infections.
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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.