ArticleScience translational medicine2024
Delayed low-dose oral administration of 4'-fluorouridine inhibits pathogenic arenaviruses in animal models of lethal disease.
Article in Science translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed.
- Favipiravir for Lassa fever: an open-label, randomized controlled phase 2 trial.Nature medicine · 2026Trial
- Towards broader-spectrum direct-acting antivirals against RNA viruses.Nature reviews. Microbiology · 2026Review
- Lassa Virus-A Persistent and Evolving Threat.Microorganisms · 2026Review
- Substrate and target selectivity of 4'-fluoroadenosine against viral and host polymerases.The Journal of biological chemistry · 2026Article
- Efficacy of an Fc-silent antibody targeting the apical domain of human transferrin receptor 1 in transgenic mouse models of Junín virus infection.Antiviral research · 2026Article
- 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
- A Transgenic Syrian Hamster Model for New World Hemorrhagic Fever Mammarenavirus Infection.Research square · 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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- Inactivation of Ebola, Nipah, and Lassa viruses in tissue using neutral buffered formalin, MagMAX lysis/binding solution, or TriPure isolation reagent.Scientific reports · 2025Article
- 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
- The oral nucleoside drug VV116 is a promising candidate for treating Nipah virus infection.Emerging microbes & infections · 2025Article
- An orally available 4Journal of virology · 2025Article
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- Lassa fever in African green monkeys: Clinical disease and fatal outcome are associated with systemic viral dissemination and inflammation.Cell reports. Medicine · 2025Article
- Henipaviruses: epidemiology, ecology, disease, and the development of vaccines and therapeutics.Clinical microbiology reviews · 2025Review
Corrections and comments
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Authors and funding
35 authors.
Funding
Abstract
Development of broad-spectrum antiviral therapies is critical for outbreak and pandemic preparedness against emerging and reemerging viruses. Viruses inducing hemorrhagic fevers cause high morbidity and mortality in humans and are associated with several recent international outbreaks, but approved therapies for treating most of these pathogens are lacking. Here, we show that 4'-fluorouridine (4'-FlU; EIDD-2749), an orally available ribonucleoside analog, has antiviral activity against multiple hemorrhagic fever viruses in cell culture, including Nipah virus, Crimean-Congo hemorrhagic fever virus, orthohantaviruses, and arenaviruses. We performed preclinical in vivo evaluation of oral 4'-FlU against two arenaviruses, Old World Lassa virus (LASV) and New World Junín virus (JUNV), in guinea pig models of lethal disease. 4'-FlU demonstrated both advantageous pharmacokinetic characteristics and high efficacy in both of these lethal disease guinea pig models. Additional experiments supported protection of the infected animals even when 4'-FlU delivery was reduced to a low dose of 0.5 milligram per kilogram. To demonstrate clinical utility, 4'-FlU treatment was evaluated when initiated late in the course of infection (12 or 9 days after infection for LASV and JUNV, respectively). Delayed treatment resulted in rapid resolution of clinical signs, demonstrating an extended window for therapeutic intervention. These data support the use of 4'-FlU as a potent and efficacious treatment against highly pathogenic arenaviruses of public health concern with a virus inhibition profile suggesting broad-spectrum utility as an orally available antiviral drug against a wide variety of viral pathogens.
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