Woolsey Courtney, Cross Robert W, Chu Victor C, Prasad Abhishek N, Agans Krystle N, Borisevich Viktoriya, Deer Daniel J, Harrison Mack B, Martinez Jasmine K, Dobias Natalie S, Fenton Karla A, Cihlar Tomas, Nguyen Anh-Quan, Babusis Darius, Bannister Roy, Vermillion Meghan S, Geisbert Thomas W
Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Sci Adv. 2025 Mar 14;11(11):eadw0659. doi: 10.1126/sciadv.adw0659.
Obeldesivir (ODV; GS-5245) is an orally administered ester prodrug of the parent nucleoside GS-441524 that has broad spectrum antiviral activity inhibiting viral RNA-dependent RNA polymerases. We recently showed that ODV completely protects cynomolgus macaques against lethal infection with Sudan virus when given 24 hours after parenteral exposure. 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.
瑞德西韦（ODV；GS-5245）是母体核苷GS-441524的口服酯前药，具有广谱抗病毒活性，可抑制病毒RNA依赖性RNA聚合酶。我们最近发现，在肠胃外暴露24小时后给予ODV，可完全保护食蟹猴免受苏丹病毒的致命感染。在此，我们报告，当在黏膜（结膜）暴露24小时后开始治疗时，对食蟹猴和恒河猴每天口服一次ODV，持续10天，分别可提供80%和100%的保护，使其免受致命的埃博拉病毒感染。ODV治疗可延迟病毒复制，减轻过度炎症反应并促进适应性免疫。对于疫情应对，口服抗病毒药物可能比目前已获批的静脉注射药物具有显著优势，如供应、储存、分发和给药都很方便。此外，这些结果支持了ODV作为一种口服暴露后预防药物的潜力，它对丝状病毒具有广谱活性。
