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

de Wit E1, Feldmann F2, Cronin J3, Jordan R4, Okumura A5, Thomas T3, Scott D2, Cihlar T4, Feldmann H3.

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

[Indexed for MEDLINE]

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