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

J Infect Dis. 2020 Nov 9;222(11):1894-1901. doi: 10.1093/infdis/jiaa290.

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.

Keywords: Marburg virus; GS-5734; filovirus; nonhuman primate; remdesivir.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Alanine / analogs & derivatives
  • Animals
  • Antimetabolites / therapeutic use*
  • Antiviral Agents / therapeutic use*
  • Disease Models, Animal
  • Female
  • Kaplan-Meier Estimate
  • Macaca fascicularis
  • Male
  • Marburg Virus Disease / drug therapy*
  • Marburg Virus Disease / mortality
  • Marburg Virus Disease / pathology
  • Marburg Virus Disease / virology
  • Marburgvirus / drug effects*
  • Monkey Diseases / drug therapy*
  • Monkey Diseases / mortality
  • Monkey Diseases / pathology
  • Monkey Diseases / virology
  • RNA, Viral

Substances

  • Antimetabolites
  • Antiviral Agents
  • RNA, Viral
  • remdesivir
  • Adenosine Monophosphate
  • Alanine