A Randomized, Blinded, Vehicle-Controlled Dose-Ranging Study to Evaluate and Characterize Remdesivir Efficacy Against Ebola Virus in Rhesus Macaques
Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure. Thirty rhesus macaques underwent surgical implantation of telemetry devices for the fine-scale monitoring of body temperature and activity, as well as central venous catheters, to enable treatment administration and blood collection. Treatment, consisting of a loading dose of RDV followed by once-daily maintenance doses for 11 days, was initiated 4 days after virus exposure when all animals were exhibiting disease signs consistent with incipient EBOV disease as well as quantifiable levels of EBOV RNA in plasma. In the RDV treatment groups receiving loading/maintenance doses of 5/2.5 mg/kg, 10/5 mg/kg, and 20/10 mg/kg, a total of 6 of 8 (75%), 7 of 8 (87.5%), and 5 of 7 (71.4%) animals survived, respectively. In the vehicle control group, one of seven animals (14.3%) survived. The improved survival rate compared to the control group was statistically significant only for the 10/5 mg/kg RDV treatment group. This treatment regimen also resulted in a significantly lower systemic viral load compared to the vehicle control after a single RDV treatment. All three RDV regimens produced a significantly lower systemic viral load after two treatments. For most animals, RDV treatment, regardless of dose, resulted in the amelioration of many of the clinical-pathological changes associated with EBOV disease in this model.
Authors
- Xiankun Zeng (ORCID: https://orcid.org/0000-0003-3526-8755)
- Christiana Blair
- Kristan A. O’Brien
- Heather L. Esham
- Alexandra N. Jay (ORCID: https://orcid.org/0000-0002-5246-6940)
- Bali Singh
- Jeffrey R. Kugelman (ORCID: https://orcid.org/0000-0001-7442-9684)
- Joshua L. Moore (ORCID: https://orcid.org/0000-0003-2233-2527)
- Charlotte Hedskog (ORCID: https://orcid.org/0000-0003-0512-7767)
- Darius Babusis (ORCID: https://orcid.org/0000-0001-5599-1671)
- Roy Bannister (ORCID: https://orcid.org/0000-0002-6311-1440)
- Jennifer L. Scruggs
- Tomáš Cihlář (ORCID: https://orcid.org/0000-0001-6840-0885)
- Franco Rossi
- Eric D. Lee (ORCID: https://orcid.org/0000-0003-2848-7298)
- Kristen Akers
- Kelly S. Wetzel
- Névéna Mollova
- Jesse Steffens
- Dawn M. Wetzel (ORCID: https://orcid.org/0000-0002-3990-7043)
- Travis K. Warren (ORCID: https://orcid.org/0000-0002-2469-6749)
- Laura Gomba
- Sean A. Van Tongeren
- Danielle Porter (ORCID: https://orcid.org/0000-0001-8459-2370)
- Elizabeth S. Brown
- Holly Bloomfield
- Sina Bavari (ORCID: https://orcid.org/0000-0001-8424-5635)
- J. Matthew Meinig (ORCID: https://orcid.org/0000-0003-2019-2890)
- Jessica M. Weidner
- Elizabeth E. Zumbrun (ORCID: https://orcid.org/0000-0002-9897-7201)
- Sarah L. Norris (ORCID: https://orcid.org/0000-0002-5393-6430)
- Carly B. Garvey (ORCID: https://orcid.org/0009-0009-2481-8900)
- Paul A. Kallgren
- Nicole L. Garza
- Jay Wells
- Theodore Bryan
- John Walters
- Ginger Lynn
- Ethan Englund
- Christie H. Scheuerell
Institutions
- Wilmington University (US)
- United States Army Medical Research Institute of Infectious Diseases (US)
- LabCorp (United States) (US)
- Gilead Sciences (United States) (US)
- The Geneva Foundation (US)
Publication Details
- Journal
- Viruses
- Published
- 2024-12-18
- DOI
- https://doi.org/10.3390/v16121934
- Citations
- 1
- Primary Topic
- Viral Infections and Outbreaks Research
- Type
- article
- Field-Weighted Citation Impact
- 0.39
Funders
- Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense