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

作者：Danielle Porter, Jessica M. Weidner, Laura Gomba, Roy Bannister, Christiana Blair, Robert Jordan, Jay Wells, Kelly S. Wetzel, Nicole L. Garza, Sean Van Tongeren, Ginger Donnelly, Jesse Steffens, Alicia M. Moreau, Jeremy J. Bearss, Eric Lee, Sina Bavari, Tomáš Cihlář, Travis K. Warren · 发表于：The Journal of Infectious Diseases · 年份：2020 · DOI：10.1093/infdis/jiaa290 · 被引用次数：82 · 研究领域：Viral Infections and Outbreaks Research、Disaster Response and Management、Hepatitis B Virus Studies

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.