ArticleJournal of virology2013
T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 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.
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.
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Who cites it
206 citing papers in PubMed, 380 citations in OpenAlex.
- Oral Favipiravir Exposure and Pharmacodynamic Effects in Adult Outpatients With Acute Influenza.The Journal of infectious diseases · 2024Trial
- Favipiravir in the Treatment of Outpatient COVID-19: A Multicenter, Randomized, Triple-Blind, Placebo-Controlled Clinical Trial.Advances in respiratory medicine · 2023Trial
- Early treatment of Favipiravir in COVID-19 patients without pneumonia: a multicentre, open-labelled, randomized control study.Emerging microbes & infections · 2022Trial
- Favipiravir Treatment of Uncomplicated Influenza in Adults: Results of Two Phase 3, Randomized, Double-Blind, Placebo-Controlled Trials.The Journal of infectious diseases · 2022Trial
- Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2022Trial
- Target-Based Antiviral Drug Development Against Human Respiratory Viruses.Pathogens (Basel, Switzerland) · 2026Review
- Recent progress in anti-Chikungunya virus drug discovery: Focus on the viral life cycle and direct-acting antivirals.Virologica Sinica · 2026Review
- Exploration of the protein and pharmacological landscape of monkeypox virus treatment: from entry point to end point.Molecular diversity · 2026Review
- Combinations of Favipiravir with Doxycycline, Azithromycin or Ivermectin Exert Synergistic Effects Against Influenza A H3N2 Virus Replication.Pathogens (Basel, Switzerland) · 2026Article
- Mechanism of SARS-CoV-2 resistance to nucleotide analog-based antivirals.Nature communications · 2026Article
- From neuraminidase inhibitors to novel mechanisms: expanding therapeutic strategies against influenza.Frontiers in cellular and infection microbiology · 2026Review
- PB1 mutations as key drivers of influenza A virus evolution.Frontiers in microbiology · 2026Review
- Strategic Preparedness of Broad-Spectrum Antivirals for Rapid Response Towards Next Pandemics.Small science · 2026Article
- A scoping review of influenza RdRp-targeting inhibitors: mechanisms, clinical translation, and emerging challenges.Frontiers in microbiology · 2026Review
- A primary oseltamivir-resistant mutation in influenza hemagglutinin and its implications for antiviral resistance surveillance.Nature communications · 2025Article
- Antiviral strategies against influenza virus: an update on approved and innovative therapeutic approaches.Cellular and molecular life sciences : CMLS · 2025Review
- Puumala orthohantavirus: prevalence, biology, disease, animal models and recent advances in therapeutics development and structural biology.Frontiers in immunology · 2025Review
- Genetic and phenotypic changes to Venezuelan equine encephalitis virus following treatment with β-D-N4-hydroxycytidine, an RNA mutagen.Scientific reports · 2024Article
- SARS-CoV-2 Resistance to Small Molecule Inhibitors.Current clinical microbiology reports · 2024Article
- N4-Hydroxycytidine/molnupiravir inhibits RNA virus-induced encephalitis by producing less fit mutated viruses.PLoS pathogens · 2024Article
146 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 1 institution in 1 country.
Funding
Abstract
Several novel anti-influenza compounds are in various phases of clinical development. One of these, T-705 (favipiravir), has a mechanism of action that is not fully understood but is suggested to target influenza virus RNA-dependent RNA polymerase. We investigated the mechanism of T-705 activity against influenza A (H1N1) viruses by applying selective drug pressure over multiple sequential passages in MDCK cells. We found that T-705 treatment did not select specific mutations in potential target proteins, including PB1, PB2, PA, and NP. Phenotypic assays based on cell viability confirmed that no T-705-resistant variants were selected. In the presence of T-705, titers of infectious virus decreased significantly (P < 0.0001) during serial passage in MDCK cells inoculated with seasonal influenza A (H1N1) viruses at a low multiplicity of infection (MOI; 0.0001 PFU/cell) or with 2009 pandemic H1N1 viruses at a high MOI (10 PFU/cell). There was no corresponding decrease in the number of viral RNA copies; therefore, specific virus infectivity (the ratio of infectious virus yield to viral RNA copy number) was reduced. Sequence analysis showed enrichment of G→A and C→T transversion mutations, increased mutation frequency, and a shift of the nucleotide profiles of individual NP gene clones under drug selection pressure. Our results demonstrate that T-705 induces a high rate of mutation that generates a nonviable viral phenotype and that lethal mutagenesis is a key antiviral mechanism of T-705. Our findings also explain the broad spectrum of activity of T-705 against viruses of multiple families.
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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.