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

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.

• Authors: Danielle P Porter, Jessica M Weidner, Laura Gomba, Roy Bannister, Christiana Blair, Robert Jordan, Jay Wells, Kelly Wetzel, Nicole Garza, Sean Van Tongeren, Ginger Donnelly, Jesse Steffens, Alicia Moreau, Jeremy Bearss, Eric Lee, Sina Bavari, Tomas Cihlar, Travis K Warren
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 222 Issue 11 Pg. 1894-1901 (11 09 2020) ISSN: 1537-6613 [Electronic] United States
• PMID: 32479636 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

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

Topics

• 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, mortality, pathology, virology)
• Marburgvirus (drug effects)
• Monkey Diseases (drug therapy, mortality, pathology, virology)
• RNA, Viral