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


Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
09 11 2020
Historique:
received: 11 02 2020
accepted: 26 05 2020
pubmed: 2 6 2020
medline: 26 3 2021
entrez: 2 6 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32479636
pii: 5849693
doi: 10.1093/infdis/jiaa290
doi:

Substances chimiques

Antimetabolites 0
Antiviral Agents 0
RNA, Viral 0
remdesivir 3QKI37EEHE
Adenosine Monophosphate 415SHH325A
Alanine OF5P57N2ZX

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1894-1901

Commentaires et corrections

Type : CommentIn

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Auteurs

Danielle P Porter (DP)

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

Jessica M Weidner (JM)

Geneva Foundation, Tacoma, Washington, USA.
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.

Laura Gomba (L)

Geneva Foundation, Tacoma, Washington, USA.
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.

Roy Bannister (R)

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

Christiana Blair (C)

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

Robert Jordan (R)

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

Jay Wells (J)

Geneva Foundation, Tacoma, Washington, USA.
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.

Kelly Wetzel (K)

Geneva Foundation, Tacoma, Washington, USA.
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.

Nicole Garza (N)

Geneva Foundation, Tacoma, Washington, USA.
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.

Sean Van Tongeren (S)

Geneva Foundation, Tacoma, Washington, USA.
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.

Ginger Donnelly (G)

Geneva Foundation, Tacoma, Washington, USA.
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.

Jesse Steffens (J)

Geneva Foundation, Tacoma, Washington, USA.
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.

Alicia Moreau (A)

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

Jeremy Bearss (J)

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

Eric Lee (E)

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

Sina Bavari (S)

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

Tomas Cihlar (T)

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

Travis K Warren (TK)

Geneva Foundation, Tacoma, Washington, USA.
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.

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Classifications MeSH