The oral drug obeldesivir protects nonhuman primates against lethal Ebola virus infection

Courtney Woolsey; Robert Cross; Victor C. Chu; Abhishek Prasad; Krystle N. Agans; Viktoriya Borisevich; Daniel J. Deer; Mack B. Harrison; Jasmine K. Martinez; Natalie S. Dobias; Karla Fenton; Tomas Cihlar; Anh Quan Nguyen; Darius Babusis; Roy Bannister; Meghan S. Vermillion; Thomas W. Geisbert

doi:10.1126/sciadv.adw0659

The oral drug obeldesivir protects nonhuman primates against lethal Ebola virus infection

Courtney Woolsey, Robert Cross, Victor C. Chu, Abhishek Prasad, Krystle N. Agans, Viktoriya Borisevich, Daniel J. Deer, Mack B. Harrison, Jasmine K. Martinez, Natalie S. Dobias, Karla Fenton, Tomas Cihlar, Anh Quan Nguyen, Darius Babusis, Roy Bannister, Meghan S. Vermillion, Thomas W. Geisbert

Microbiology And Immunology

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Abstract

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.

Original language	English (US)
Article number	eadw0659
Journal	Science Advances
Volume	11
Issue number	11
DOIs	https://doi.org/10.1126/sciadv.adw0659
State	Published - Mar 14 2025

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Woolsey, C., Cross, R., Chu, V. C., Prasad, A., Agans, K. N., Borisevich, V., Deer, D. J., Harrison, M. B., Martinez, J. K., Dobias, N. S., Fenton, K., Cihlar, T., Nguyen, A. Q., Babusis, D., Bannister, R., Vermillion, M. S., & Geisbert, T. W. (2025). The oral drug obeldesivir protects nonhuman primates against lethal Ebola virus infection. Science Advances, 11(11), Article eadw0659. https://doi.org/10.1126/sciadv.adw0659

Woolsey, C , Cross, R, Chu, VC, Prasad, A, Agans, KN, Borisevich, V, Deer, DJ, Harrison, MB, Martinez, JK, Dobias, NS, Fenton, K, Cihlar, T, Nguyen, AQ, Babusis, D, Bannister, R, Vermillion, MS & Geisbert, TW 2025, 'The oral drug obeldesivir protects nonhuman primates against lethal Ebola virus infection', Science Advances, vol. 11, no. 11, eadw0659. https://doi.org/10.1126/sciadv.adw0659

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abstract = "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.",

author = "Courtney Woolsey and Robert Cross and Chu, {Victor C.} and Abhishek Prasad and Agans, {Krystle N.} and Viktoriya Borisevich and Deer, {Daniel J.} and Harrison, {Mack B.} and Martinez, {Jasmine K.} and Dobias, {Natalie S.} and Karla Fenton and Tomas Cihlar and Nguyen, {Anh Quan} and Darius Babusis and Roy Bannister and Vermillion, {Meghan S.} and Geisbert, {Thomas W.}",

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The oral drug obeldesivir protects nonhuman primates against lethal Ebola virus infection

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