ArticleAntimicrobial agents and chemotherapy2015
Biochemical Evaluation of the Inhibition Properties of Favipiravir and 2'-C-Methyl-Cytidine Triphosphates against Human and Mouse Norovirus RNA Polymerases.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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
37 citing papers in PubMed, 65 citations in OpenAlex.
- Mechanism and spectrum of inhibition of viral polymerases by 2'-deoxy-2'-β-fluoro-4'-azidocytidine or azvudine.NAR molecular medicine · 2025Article
- Human norovirus cultivation systems and their use in antiviral research.Journal of virology · 2024Review
- Favipiravir induces HuNoV viral mutagenesis and infectivity loss with clinical improvement in immunocompromised patients.Clinical immunology (Orlando, Fla.) · 2024Article
- Antiviral agents and disinfectants for foot‑and‑mouth disease (Review).Biomedical reports · 2023Review
- A comprehensive update on the structure and synthesis of potential drug targets for combating the coronavirus pandemic caused by SARS-CoV-2.Archiv der Pharmazie · 2022Review
- Enhancing the Antiviral Potency of Nucleobases for Potential Broad-Spectrum Antiviral Therapies.Viruses · 2021Article
- Current and Future Antiviral Strategies to Tackle Gastrointestinal Viral Infections.Microorganisms · 2021Review
- Nucleoside Analogs and Nucleoside Precursors as Drugs in the Fight against SARS-CoV-2 and Other Coronaviruses.Molecules (Basel, Switzerland) · 2021Review
- Efficacy and Safety of New and Emerging Drugs for COVID-19: Favipiravir and Dexamethasone.Current pharmacology reports · 2021Review
- Application of Molecular Dynamics Simulations to the Design of Nucleotide Inhibitors Binding to Norovirus Polymerase.Journal of chemical information and modeling · 2020Article
- 2'-Fluoro-2'-deoxycytidine inhibits murine norovirus replication and synergizes MPA, ribavirin and T705.Archives of virology · 2020Article
- The Impact of the COVID-19 "Infodemic" on Drug-Utilization Behaviors: Implications for Pharmacovigilance.Drug safety · 2020Article
- Independent inhibition of the polymerase and deubiquitinase activities of the Crimean-Congo Hemorrhagic Fever Virus full-length L-protein.PLoS neglected tropical diseases · 2020Article
- COVID-19 Outbreak: Pathogenesis, Current Therapies, and Potentials for Future Management.Frontiers in pharmacology · 2020Review
- A new antiviral scaffold for human norovirus identified with computer-aided approaches on the viral polymerase.Scientific reports · 2019Article
- New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections.Chemistry, an Asian journal · 2019Review
- 2'-C-methylated nucleotides terminate virus RNA synthesis by preventing active site closure of the viral RNA-dependent RNA polymerase.The Journal of biological chemistry · 2019Article
- Norovirus in health care and implications for the immunocompromised host.Current opinion in infectious diseases · 2019Article
- The Adenosine Analogue NITD008 has Potent Antiviral Activity against Human and Animal Caliciviruses.Viruses · 2019Article
- Norovirus antivirals: Where are we now?Medicinal research reviews · 2019Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Norovirus (NoV) is a positive-sense single-stranded RNA virus that causes acute gastroenteritis and is responsible for 200,000 deaths per year worldwide. No effective vaccine or treatment is available. Recent studies have shown that the nucleoside analogs favipiravir (T-705) and 2'-C-methyl-cytidine (2CM-C) inhibit NoV replication in vitro and in animal models, but their precise mechanism of action is unknown. We evaluated the molecular interactions between nucleoside triphosphates and NoV RNA-dependent RNA polymerase (NoVpol), the enzyme responsible for replication and transcription of NoV genomic RNA. We found that T-705 ribonucleoside triphosphate (RTP) and 2CM-C triphosphate (2CM-CTP) equally inhibited human and mouse NoVpol activities at concentrations resulting in 50% of maximum inhibition (IC50s) in the low micromolar range. 2CM-CTP inhibited the viral polymerases by competing directly with natural CTP during primer elongation, whereas T-705 RTP competed mostly with ATP and GTP at the initiation and elongation steps. Incorporation of 2CM-CTP into viral RNA blocked subsequent RNA synthesis, whereas T-705 RTP did not cause immediate chain termination of NoVpol. 2CM-CTP and T-705 RTP displayed low levels of enzyme selectivity, as they were both recognized as substrates by human mitochondrial RNA polymerase. The level of discrimination by the human enzyme was increased with a novel analog of T-705 RTP containing a 2'-C-methyl substitution. Collectively, our data suggest that 2CM-C inhibits replication of NoV by acting as a classic chain terminator, while T-705 may inhibit the virus by multiple mechanisms of action. Understanding the precise mechanism of action of anti-NoV compounds could provide a rational basis for optimizing their inhibition potencies and selectivities.
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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.