Oral administration of obeldesivir protects nonhuman primates against Sudan ebolavirus

• 成果类型: Article
• 署名作者: Cross, Robert W.; Woolsey, Courtney; Chu, Victor C.; Babusis, Darius; Bannister, Roy; Vermillion, Meghan S.; Geleziunas, Romas; Barrett, Kimberly T.; Bunyan, Elaine; Nguyen, Anh-Quan; Cihlar, Tomas; Porter, Danielle P.; Prasad, Abhishek N.; Deer, Daniel J.; Borisevich, Viktoriya; Agans, Krystle N.; Martinez, Jasmine; Harrison, Mack B.; Dobias, Natalie S.; Fenton, Karla A.; Bilello, John P.; Geisbert, Thomas W.
• 署名单位: University of Texas System; University of Texas Medical Branch Galveston; University of Texas System; University of Texas Medical Branch Galveston; Gilead Sciences
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11646
• DOI: 10.1126/science.adk6176
• 发表日期: 2024-03-15
• 关键词: marburg virus; antibody cocktail

摘要

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.