ArticlePloS one2013
The ambiguous base-pairing and high substrate efficiency of T-705 (Favipiravir) Ribofuranosyl 5'-triphosphate towards influenza A virus polymerase.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 1 of them a synthesis that pooled it.
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Who cites it
142 citing papers in PubMed, 1 synthesis or guideline pooled it, 267 citations in OpenAlex.
- A Systematic Review of the Global Intervention for SARS-CoV-2 Combating: From Drugs Repurposing to Molnupiravir Approval.Drug design, development and therapy · 2022Pooled it
- Oral Favipiravir Exposure and Pharmacodynamic Effects in Adult Outpatients With Acute Influenza.The Journal of infectious diseases · 2024Trial
- Highly effective viral RdRP translocation hindrance by the remdesivir nucleotide.Nucleic acids research · 2026Article
- Mechanism of SARS-CoV-2 resistance to nucleotide analog-based antivirals.Nature communications · 2026Article
- A scoping review of influenza RdRp-targeting inhibitors: mechanisms, clinical translation, and emerging challenges.Frontiers in microbiology · 2026Review
- From neuraminidase inhibitors to novel mechanisms: expanding therapeutic strategies against influenza.Frontiers in cellular and infection microbiology · 2026Review
- Emerging Strategies and Progress in the Medical Management of Marburg Virus Disease.Pathogens (Basel, Switzerland) · 2025Review
- Puumala orthohantavirus: prevalence, biology, disease, animal models and recent advances in therapeutics development and structural biology.Frontiers in immunology · 2025Review
- An adenosine analog shows high antiviral potency against coronavirus and arenavirus mainly through an unusual base pairing mode.Nature communications · 2024Article
- Navigating the COVID-19 Therapeutic Landscape: Unveiling Novel Perspectives on FDA-Approved Medications, Vaccination Targets, and Emerging Novel Strategies.Molecules (Basel, Switzerland) · 2024Review
- SARS-CoV-2 Resistance to Small Molecule Inhibitors.Current clinical microbiology reports · 2024Article
- Pharmacogenomic Studies of Antiviral Drug Favipiravir.Pharmaceutics · 2024Article
- Favipiravir Suppresses Zika Virus (ZIKV) through Activity as a Mutagen.Microorganisms · 2023Article
- Potential treatments of COVID-19: Drug repurposing and therapeutic interventions.Journal of pharmacological sciences · 2023Review
- Synthesis and Behavior of DNA Oligomers Containing the Ambiguous Z-Nucleobase 5-Aminoimidazole-4-carboxamide.Molecules (Basel, Switzerland) · 2023Article
- Kill or corrupt: Mechanisms of action and drug-resistance of nucleotide analogues against SARS-CoV-2.Antiviral research · 2023Review
- Combating Lassa Fever in West African Sub-Region: Progress, Challenges, and Future Perspectives.Viruses · 2023Review
- Current understanding of nucleoside analogs inhibiting the SARS-CoV-2 RNA-dependent RNA polymerase.Computational and structural biotechnology journal · 2023Review
- COVID-19 Therapeutics: Use, Mechanism of Action, and Toxicity (Xenobiotics).Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2023Review
- Nucleoside analogs for management of respiratory virus infections: mechanism of action and clinical efficacy.Current opinion in virology · 2022Review
82 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-705 (Favipiravir) is a broad-spectrum antiviral molecule currently in late stage clinical development for the treatment of influenza virus infection. Although it is believed that T-705 potency is mediated by its ribofuranosyl triphosphate (T-705 RTP) metabolite that could be mutagenic, the exact molecular interaction with the polymerase of influenza A virus (IAVpol) has not been elucidated. Here, we developed a biochemical assay to measure the kinetics of nucleotide incorporation by IAVpol in the elongation mode. In this assay, T-705 RTP was recognized by IAVpol as an efficient substrate for incorporation to the RNA both as a guanosine and an adenosine analog. Compared to natural GTP and ATP, the discrimination of T-705 RTP was about 19- and 30-fold, respectively. Although the single incorporation of the ribonucleotide monophosphate form of T-705 did not efficiently block RNA synthesis, two consecutive incorporation events prevented further primer extension. In comparison, 3'-deoxy GTP caused immediate chain termination but was incorporated less efficiently by the enzyme, with a discrimination of 4,900-fold relative to natural GTP. Collectively, these results provide the first detailed biochemical characterization to evaluate the substrate efficiency and the inhibition potency of nucleotide analogs against influenza virus polymerase. The combination of ambiguous base-pairing with low discrimination of T-705 RTP provides a mechanistic basis for the in vitro mutagenic effect of T-705 towards influenza virus.
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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.