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Here, we report that once daily oral ODV treatment of cynomolgus and rhesus macaques for 10 days confers 80 and 100% protection, respectively, against lethal Ebola virus infection when treatment is initiated 24 hours after mucosal (conjunctival) exposure. ODV treatment delayed viral replication to abate excessive inflammation and promote adaptive immunity. For outbreak response, oral antivirals might present substantial advantages over now approved intravenous drugs, such as easy supply, storage, distribution, and administration. Furthermore, these results support the potential of ODV as an oral postexposure prophylaxis with broad spectrum activity across filoviruses.<\/jats:p>","DOI":"10.1126\/sciadv.adw0659","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T17:58:26Z","timestamp":1741975106000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":27,"title":["The oral drug obeldesivir protects nonhuman primates against lethal Ebola virus infection"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3389-0137","authenticated-orcid":true,"given":"Courtney","family":"Woolsey","sequence":"first","affiliation":[{"name":"Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA."},{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 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