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4'-Fluorouridine is an oral antiviral that blocks respiratory syncytial virus and SARS-CoV-2 replication.
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.
  • Sourimant J; Center for Translational Antiviral Research, Georgia State University, Atlanta, GA 30303, USA.
  • Lieber CM; Center for Translational Antiviral Research, Georgia State University, Atlanta, GA 30303, USA.
  • Aggarwal M; Center for Translational Antiviral Research, Georgia State University, Atlanta, GA 30303, USA.
  • Cox RM; Center for Translational Antiviral Research, Georgia State University, Atlanta, GA 30303, USA.
  • Wolf JD; Center for Translational Antiviral Research, Georgia State University, Atlanta, GA 30303, USA.
  • Yoon JJ; Center for Translational Antiviral Research, Georgia State University, Atlanta, GA 30303, USA.
  • Toots M; Center for Translational Antiviral Research, Georgia State University, Atlanta, GA 30303, USA.
  • Ye C; Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
  • Sticher Z; Emory Institute for Drug Development, Emory University, Atlanta, GA 30322, USA.
  • Kolykhalov AA; Emory Institute for Drug Development, Emory University, Atlanta, GA 30322, USA.
  • Martinez-Sobrido L; Drug Innovation Ventures at Emory (DRIVE), Atlanta, GA 30322, USA.
  • Bluemling GR; Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
  • Natchus MG; Emory Institute for Drug Development, Emory University, Atlanta, GA 30322, USA.
  • Painter GR; Drug Innovation Ventures at Emory (DRIVE), Atlanta, GA 30322, USA.
  • Plemper RK; Emory Institute for Drug Development, Emory University, Atlanta, GA 30322, USA.
Science ; 375(6577): 161-167, 2022 Jan 14.
Article in English | MEDLINE | ID: covidwho-1648160
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Uracil Nucleotides / Respiratory Syncytial Virus, Human / Respiratory Syncytial Virus Infections / SARS-CoV-2 / COVID-19 Topics: Variants Limits: Animals / Female / Humans Language: English Journal: Science Year: 2022 Document Type: Article Affiliation country: Science.abj5508

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Uracil Nucleotides / Respiratory Syncytial Virus, Human / Respiratory Syncytial Virus Infections / SARS-CoV-2 / COVID-19 Topics: Variants Limits: Animals / Female / Humans Language: English Journal: Science Year: 2022 Document Type: Article Affiliation country: Science.abj5508