ArticlePLoS pathogens2023
4'-Fluorouridine mitigates lethal infection with pandemic human and highly pathogenic avian influenza viruses.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 36 citations in OpenAlex.
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- Updated A(H1N1)pdm09 influenza virus ferret infection model permits refined antiviral assessment using aerosol inhalation challenge.PLoS pathogens · 2026Article
- From Hepatitis to Encephalitis: Neuroinvasion and Antiviral Development in Rift Valley Fever Virus Infection.Pathogens (Basel, Switzerland) · 2026Review
- Substrate and target selectivity of 4'-fluoroadenosine against viral and host polymerases.The Journal of biological chemistry · 2026Article
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- The oral nucleoside analogue inhibitor VV251 effectively inhibits coinfection by respiratory syncytial virus and influenza A virus.Journal of virology · 2026Article
- Efficacy of the nucleoside analog 4'-Fluorouridine against Nipah virus in the Syrian hamster model.PLoS pathogens · 2026Article
- Oral 4'fluorouridine provides postexposure protection against lethal Nipah virus infection.bioRxiv : the preprint server for biology · 2026Article
- Impact of mutations affecting 4'-fluorouridine susceptibility on fitness and treatment outcomes for Venezuelan equine encephalitis virus.Journal of virology · 2026Article
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- Segmented filamentous bacteria reprogramming of alveolar macrophages limits postinfluenza bacterial pneumonia.Science immunology · 2026Article
- Avian influenza virus H5N1 and H9N2 subtypes in different birds and humans: Findings from an extensive evaluation.Open veterinary journal · 2026Review
- Oral VV261 administration protects mice from lethal Crimean-Congo hemorrhagic fever virus challenge.Journal of virology · 2025Article
- Pathogenesis of Hazara orthonairovirus infection in type I interferon receptor-deficient mice and resolution of disease following 4'-fluorouridine therapy.Journal of virology · 2025Article
- Status of advanced respiratory syncytial virus antiviral therapeutics 2025.Current opinion in virology · 2025Review
- An orally available 4Journal of virology · 2025Article
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- Mechanism and spectrum of inhibition of viral polymerases by 2'-deoxy-2'-β-fluoro-4'-azidocytidine or azvudine.NAR molecular medicine · 2025Article
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Influenza outbreaks are associated with substantial morbidity, mortality and economic burden. Next generation antivirals are needed to treat seasonal infections and prepare against zoonotic spillover of avian influenza viruses with pandemic potential. Having previously identified oral efficacy of the nucleoside analog 4'-Fluorouridine (4'-FlU, EIDD-2749) against SARS-CoV-2 and respiratory syncytial virus (RSV), we explored activity of the compound against seasonal and highly pathogenic influenza (HPAI) viruses in cell culture, human airway epithelium (HAE) models, and/or two animal models, ferrets and mice, that assess IAV transmission and lethal viral pneumonia, respectively. 4'-FlU inhibited a panel of relevant influenza A and B viruses with nanomolar to sub-micromolar potency in HAE cells. In vitro polymerase assays revealed immediate chain termination of IAV polymerase after 4'-FlU incorporation, in contrast to delayed chain termination of SARS-CoV-2 and RSV polymerase. Once-daily oral treatment of ferrets with 2 mg/kg 4'-FlU initiated 12 hours after infection rapidly stopped virus shedding and prevented transmission to untreated sentinels. Treatment of mice infected with a lethal inoculum of pandemic A/CA/07/2009 (H1N1)pdm09 (pdmCa09) with 4'-FlU alleviated pneumonia. Three doses mediated complete survival when treatment was initiated up to 60 hours after infection, indicating a broad time window for effective intervention. Therapeutic oral 4'-FlU ensured survival of animals infected with HPAI A/VN/12/2003 (H5N1) and of immunocompromised mice infected with pdmCa09. Recoverees were protected against homologous reinfection. This study defines the mechanistic foundation for high sensitivity of influenza viruses to 4'-FlU and supports 4'-FlU as developmental candidate for the treatment of seasonal and pandemic influenza.
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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 Socratic graph.