| Literature DB >> 34855509 |
Julien Sourimant1, Carolin M Lieber1, Megha Aggarwal1, Robert M Cox1, Josef D Wolf1, Jeong-Joong Yoon1, Mart Toots1, Chengin Ye2, Zachary Sticher3, Alexander A Kolykhalov3,4, Luis Martinez-Sobrido2, Gregory R Bluemling3,4, Michael G Natchus3, George R Painter3,4,5, Richard K Plemper1,6.
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.Entities:
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Year: 2021 PMID： 34855509 PMCID： PMC9206510 DOI： 10.1126/science.abj5508
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714