2. Academic Validation
  3. 4'-Fluorouridine is an oral antiviral that blocks respiratory syncytial virus and SARS-CoV-2 replication

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

  • Science. 2022 Jan 14;375(6577):161-167. doi: 10.1126/science.abj5508.
Julien Sourimant 1,  Carolin M Lieber 1,  Megha Aggarwal 1,  Robert M Cox 1,  Josef D Wolf 1,  Jeong-Joong Yoon 1,  Mart Toots 1,  Chengin Ye 2,  Zachary Sticher 3,  Alexander A Kolykhalov 3 4,  Luis Martinez-Sobrido 2,  Gregory R Bluemling 3 4,  Michael G Natchus 3,  George R Painter 3 4 5,  Richard K Plemper 1 6
Affiliations

Affiliations

  • 1 Center for Translational Antiviral Research, Georgia State University, Atlanta, GA 30303, USA.
  • 2 Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
  • 3 Emory Institute for Drug Development, Emory University, Atlanta, GA 30322, USA.
  • 4 Drug Innovation Ventures at Emory (DRIVE), Atlanta, GA 30322, USA.
  • 5 Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • 6 Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
PMID: 34855509 DOI: 10.1126/science.abj5508
Abstract

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 older adults. We describe 4′-fluorouridine (4′-FlU, EIDD-2749), a ribonucleoside analog that inhibits RSV, related RNA viruses, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with high selectivity index in cells and human airway epithelia organoids. Polymerase inhibition within in vitro RNA-dependent RNA polymerase assays established for RSV and SARS-CoV-2 revealed transcriptional stalling after incorporation. Once-daily oral treatment was highly efficacious at 5 milligrams per kilogram (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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