Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection.


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
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

6771-6776

Déclaration 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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Auteurs

Emmie de Wit (E)

Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840; Emmie.deWit@nih.gov.

Friederike Feldmann (F)

Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.

Jacqueline Cronin (J)

Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.

Robert Jordan (R)

Biology Department, Gilead Sciences, Foster City, CA 94404.

Atsushi Okumura (A)

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032.

Tina Thomas (T)

Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.

Dana Scott (D)

Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.

Tomas Cihlar (T)

Biology Department, Gilead Sciences, Foster City, CA 94404.

Heinz Feldmann (H)

Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.

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Classifications MeSH