Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection.
Adenosine Monophosphate
/ analogs & derivatives
Alanine
/ analogs & derivatives
Animals
Antiviral Agents
/ pharmacology
Betacoronavirus
COVID-19
Coronavirus Infections
/ drug therapy
Disease Models, Animal
Lung
/ pathology
Macaca mulatta
Male
Middle East Respiratory Syndrome Coronavirus
/ drug effects
Pandemics
Pneumonia, Viral
Post-Exposure Prophylaxis
SARS-CoV-2
Viral Load
Virus Replication
/ drug effects
MERS-CoV
animal model
antiviral
remdesivir
therapy
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
24 03 2020
24 03 2020
Historique:
pubmed:
15
2
2020
medline:
2
4
2020
entrez:
15
2
2020
Statut:
ppublish
Résumé
The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV-induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.
Identifiants
pubmed: 32054787
pii: 1922083117
doi: 10.1073/pnas.1922083117
pmc: PMC7104368
doi:
Substances chimiques
Antiviral Agents
0
remdesivir
3QKI37EEHE
Adenosine Monophosphate
415SHH325A
Alanine
OF5P57N2ZX
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
6771-6776Déclaration de conflit d'intérêts
Competing interest statement: The authors affiliated with Gilead Sciences are employees of the company and may own company stock; R.J. holds a patent on the use of remdesivir to treat Filovirus infections. The authors affiliated with NIH have no conflict of interest to report.
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