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Updated: Nov 4, 2025
Generation, Amplification, and Titration of Recombinant Respiratory Syncytial Viruses
Published on: April 4, 2019
4'-Fluorouridine is a broad-spectrum orally efficacious antiviral blocking respiratory syncytial virus and SARS-CoV-2
Insights
A new drug, 4'-fluorouridine (4'-FlU), shows promise as a broad-spectrum antiviral. It effectively treats respiratory syncytial virus (RSV) and SARS-CoV-2 infections in animal models.
Area of Science:
- Virology
- Drug Discovery
- Antiviral Therapeutics
Background:
- The COVID-19 pandemic highlighted the urgent need for broad-spectrum antiviral medications against respiratory viruses.
- Respiratory syncytial virus (RSV) poses a significant health risk, particularly to children and the elderly.
Approach:
- This study introduces 4 -fluorouridine (4 -FlU, EIDD-2749), a novel ribonucleoside analog.
- 4 -FlU demonstrated potent inhibition of RSV, SARS-CoV-2, and other RNA viruses in cellular and human airway epithelial models.
- In vitro RdRP assays revealed that 4 -FlU induces transcriptional pauses in viral polymerases.
Key Points:
- Oral administration of 4 -FlU proved highly effective in preclinical models of RSV and SARS-CoV-2 infection.
- Treatment efficacy was observed in RSV-infected mice and SARS-CoV-2-infected ferrets.
- The drug was administered once daily, with treatment initiation at 24 hours post-RSV infection and 12 hours post-SARS-CoV-2 infection.
Conclusions:
- 4 -fluorouridine exhibits a high selectivity index, indicating a favorable safety profile.
- These findings position 4 -FlU as a promising broad-spectrum therapeutic candidate for multiple RNA virus infections.
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 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 well-differentiated human airway epithelia. Polymerase inhibition in in vitro RdRP assays established for RSV and SARS-CoV-2 revealed transcriptional pauses at positions i or i +3/4 post-incorporation. Once-daily oral treatment was highly efficacious at 5 mg/kg in RSV-infected mice or 20 mg/kg in ferrets infected with SARS-CoV-2 WA1/2020 or variant-of-concern (VoC) isolate CA/2020, 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.
One-Sentence Summary:
4'-Fluorouridine is an orally available ribonucleoside analog that efficiently treats RSV and SARS-CoV-2 infections in vivo .
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