Oral administration of obeldesivir protects nonhuman primates against Sudan ebolavirus

Robert Cross, Courtney Woolsey, Victor C. Chu, Darius Babusis, Roy Bannister, Meghan S. Vermillion, Romas Geleziunas, Kimberly T. Barrett, Elaine Bunyan, Anh Quan Nguyen, Tomas Cihlar, Danielle P. Porter, Abhishek Prasad, Daniel J. Deer, Viktoriya Borisevich, Krystle N. Agans, Jasmine Martinez, Mack B. Harrison, Natalie S. Dobias, Karla A. FentonJohn P. Bilello, Thomas W. Geisbert

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Obeldesivir (ODV, GS-5245) is an orally administered prodrug of the parent nucleoside of remdesivir (RDV) and is presently in phase 3 trials for COVID-19 treatment. In this work, we show that ODV and its circulating parent nucleoside metabolite, GS-441524, have similar in vitro antiviral activity against filoviruses, including Marburg virus, Ebola virus, and Sudan virus (SUDV). We also report that once-daily oral ODV treatment of cynomolgus monkeys for 10 days beginning 24 hours after SUDV exposure confers 100% protection against lethal infection. Transcriptomics data show that ODV treatment delayed the onset of inflammation and correlated with antigen presentation and lymphocyte activation. Our results offer promise for the further development of ODV to control outbreaks of filovirus disease more rapidly.

Original languageEnglish (US)
Article numbereadk6176
JournalScience
Volume383
Issue number6688
DOIs
StatePublished - Mar 15 2024

ASJC Scopus subject areas

  • General

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