4′-Fluorouridine is an oral antiviral that blocks respiratory syncytial virus and SARS-CoV-2 replication

The COVID-19 pandemic has underscored the critical need for broad-spectrum therapeutics against respiratory viruses. Respiratory syncytial virus (RSV) is a major threat to pediatric patients and the elderly. We describe 4′-fluorouridine (4′-FlU, EIDD-2749), a ribonucleoside analog that inhibits RSV,...

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Detalles Bibliográficos
Autores principales: Sourimant, Julien, Lieber, Carolin M., Aggarwal, Megha, Cox, Robert M., Wolf, Josef D., Yoon, Jeong-Joong, Toots, Mart, Ye, Chengin, Sticher, Zachary, Kolykhalov, Alexander A., Martinez-Sobrido, Luis, Bluemling, Gregory R., Natchus, Michael G., Painter, George R., Plemper, Richard K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206510/
https://www.ncbi.nlm.nih.gov/pubmed/34855509
http://dx.doi.org/10.1126/science.abj5508
Descripción
Sumario:The COVID-19 pandemic has underscored the critical need for broad-spectrum therapeutics against respiratory viruses. Respiratory syncytial virus (RSV) is a major threat to pediatric patients and the elderly. We describe 4′-fluorouridine (4′-FlU, EIDD-2749), a ribonucleoside analog that inhibits RSV, related RNA viruses, and SARS-CoV-2 with high selectivity index in cells and human airway epithelia organoids. Polymerase inhibition within in vitro RdRP assays established for RSV and SARS-CoV-2 revealed transcriptional stalling after incorporation. Once-daily oral treatment was highly efficacious at 5 mg/kg in RSV-infected mice or 20 mg/kg in ferrets infected with different SARS-CoV-2 variants-of-concern, initiated 24 or 12 hours after infection, respectively. These properties define 4′-FlU as a broad-spectrum candidate for the treatment of RSV, SARS-CoV-2, and related RNA virus infections.

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