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Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6771-6776. doi: 10.1073/pnas.1922083117. Epub 2020 Feb 13.

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

Author information

1
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840; Emmie.deWit@nih.gov.
2
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.
3
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.
4
Biology Department, Gilead Sciences, Foster City, CA 94404.
5
Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032.

Abstract

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.

KEYWORDS:

MERS-CoV; animal model; antiviral; remdesivir; therapy

PMID:
32054787
DOI:
10.1073/pnas.1922083117

Conflict of interest statement

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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