ArticleProceedings of the National Academy of Sciences of the United States of America2018
The mechanism of resistance to favipiravir in influenza.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers, 1 of them a synthesis that pooled it.
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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
185 citing papers in PubMed, 1 synthesis or guideline pooled it, 311 citations in OpenAlex.
- Emerging trends and hotspots in Oseltamivir resistance: insights from a bibliometric investigation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Pooled it
- Favipiravir Treatment of Uncomplicated Influenza in Adults: Results of Two Phase 3, Randomized, Double-Blind, Placebo-Controlled Trials.The Journal of infectious diseases · 2022Trial
- Metal-decorated graphdiyne nanocarriers for favipiravir delivery: a DFT investigation.Nanoscale advances · 2026Article
- A nanobody-based proteolysis-targeting chimera offers broad-spectrum protection against diverse influenza virus infections.Signal transduction and targeted therapy · 2026Article
- Baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating lethal influenza A(H5N1) HA clade 2.3.4.4b infection in mice.Nature communications · 2026Article
- Combinations of Favipiravir with Doxycycline, Azithromycin or Ivermectin Exert Synergistic Effects Against Influenza A H3N2 Virus Replication.Pathogens (Basel, Switzerland) · 2026Article
- Anti-influenza drugs targeting trimeric RNA polymerase complex: From development to clinics.Acta pharmaceutica Sinica. B · 2026Review
- Genetic characterization and whole-genome sequencing-based genetic analysis of influenza B in Shandong Province during 2015-2024.Scientific reports · 2026Article
- Mutation rate variability in viral populations: Implications for lethal mutagenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A scoping review of influenza RdRp-targeting inhibitors: mechanisms, clinical translation, and emerging challenges.Frontiers in microbiology · 2026Review
- Computational Structural Analysis Predicts Host-Range Promiscuity and Antiviral Resistance in North American H5N1 Lineages.Computational and structural biotechnology journal · 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
- Trends, Gaps, and Challenges in Antiviral Resistance: A Bibliometric Analysis and Narrative Synthesis of Key Viruses, Resistance Mechanisms, and Drivers.BioMed research international · 2026Article
- Orchestrating immunopathology: the spectrum of programmed cell death pathways co-opted by influenza a virus in pulmonary immunity.Frontiers in immunology · 2026Review
- Nanchangmycin suppresses influenza A virus infection by blocking endosomal acidification.Acta biochimica et biophysica Sinica · 2025Article
- Article
- Strategies and efforts in circumventing the emergence of antiviral resistance against conventional antivirals.npj antimicrobials and resistance · 2025Review
- Multiple antiviral mechanisms of Ephedrae Herba and Cinnamomi Cortex against influenza: inhibition of entry and replication.Microbiology spectrum · 2025Article
- Evaluating the Potential Adverse Effects of Favipiravir on Biochemical, Histopathological, and Spermatological Parameters in Male Rats' Testicular Tissue.Journal of biochemical and molecular toxicology · 2025Article
125 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Favipiravir is a broad-spectrum antiviral that has shown promise in treatment of influenza virus infections. While emergence of resistance has been observed for many antiinfluenza drugs, to date, clinical trials and laboratory studies of favipiravir have not yielded resistant viruses. Here we show evolution of resistance to favipiravir in the pandemic H1N1 influenza A virus in a laboratory setting. We found that two mutations were required for robust resistance to favipiravir. We demonstrate that a K229R mutation in motif F of the PB1 subunit of the influenza virus RNA-dependent RNA polymerase (RdRP) confers resistance to favipiravir in vitro and in cell culture. This mutation has a cost to viral fitness, but fitness can be restored by a P653L mutation in the PA subunit of the polymerase. K229R also conferred favipiravir resistance to RNA polymerases of other influenza A virus strains, and its location within a highly conserved structural feature of the RdRP suggests that other RNA viruses might also acquire resistance through mutations in motif F. The mutations identified here could be used to screen influenza virus-infected patients treated with favipiravir for the emergence of resistance.
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What OpenQuestion holds
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.