Oral administration of obeldesivir protects nonhuman primates against <i>Sudan ebolavirus</i>-Reference-Cited by-同舟云学术

Oral administration of obeldesivir protects nonhuman primates against Sudan ebolavirus

Published:2024-03-15 Issue:6688 Volume:383 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Cross Robert W.¹²^ORCID,Woolsey Courtney¹²^ORCID,Chu Victor C.³^ORCID,Babusis Darius³^ORCID,Bannister Roy³^ORCID,Vermillion Meghan S.³^ORCID,Geleziunas Romas³,Barrett Kimberly T.³^ORCID,Bunyan Elaine³^ORCID,Nguyen Anh-Quan³^ORCID,Cihlar Tomas³,Porter Danielle P.³^ORCID,Prasad Abhishek N.¹²^ORCID,Deer Daniel J.¹²^ORCID,Borisevich Viktoriya¹²,Agans Krystle N.¹²^ORCID,Martinez Jasmine¹²^ORCID,Harrison Mack B.¹²^ORCID,Dobias Natalie S.¹²^ORCID,Fenton Karla A.¹²^ORCID,Bilello John P.³^ORCID,Geisbert Thomas W.¹²^ORCID

Affiliation:

1. Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.

2. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.

3. Gilead Sciences, Inc., Foster City, CA, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adk6176

Reference57 articles.

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