Remdesivir (GS-5734) Is Efficacious in Cynomolgus Macaques Infected With Marburg Virus

Author:

Porter Danielle P1,Weidner Jessica M23,Gomba Laura23,Bannister Roy1,Blair Christiana1,Jordan Robert1,Wells Jay23,Wetzel Kelly23,Garza Nicole23,Van Tongeren Sean23,Donnelly Ginger23,Steffens Jesse23,Moreau Alicia3,Bearss Jeremy3,Lee Eric3,Bavari Sina3,Cihlar Tomas1,Warren Travis K23

Affiliation:

1. Gilead Sciences Inc., Foster City, California, USA

2. Geneva Foundation, Tacoma, Washington, USA

3. United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA

Abstract

Abstract Marburg virus (MARV) is a filovirus with documented human case-fatality rates of up to 90%. Here, we evaluated the therapeutic efficacy of remdesivir (GS-5734) in nonhuman primates experimentally infected with MARV. Beginning 4 or 5 days post inoculation, cynomolgus macaques were treated once daily for 12 days with vehicle, 5 mg/kg remdesivir, or a 10-mg/kg loading dose followed by 5 mg/kg remdesivir. All vehicle-control animals died, whereas 83% of animals receiving a 10-mg/kg loading dose of remdesivir survived, as did 50% of animals receiving a 5-mg/kg remdesivir regimen. Remdesivir-treated animals exhibited improved clinical scores, lower plasma viral RNA, and improved markers of kidney function, liver function, and coagulopathy versus vehicle-control animals. The small molecule remdesivir showed therapeutic efficacy in this Marburg virus disease model with treatment initiation 5 days post inoculation, supporting further assessment of remdesivir for the treatment of Marburg virus disease in humans.

Funder

US Army Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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