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

Middle East respiratory syndrome coronavirusCase fatality rateMedicineContext (archaeology)Rhesus macaqueVirologyMacaqueImmunologyViral replicationLungRespiratory systemCoronavirusClinical trialVirusCoronavirus disease 2019 (COVID-19)PathologyDiseaseInternal medicineBiologyInfectious disease (medical specialty)Epidemiology

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Year
2020
Type
article
Volume
117
Issue
12
Pages
6771-6776
Citations
927
Access
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Emmie de Wit, Friederike Feldmann, Jacqueline Cronin et al. (2020). Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proceedings of the National Academy of Sciences , 117 (12) , 6771-6776. https://doi.org/10.1073/pnas.1922083117

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DOI
10.1073/pnas.1922083117