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

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

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / pharmacology
  • Alanine / analogs & derivatives*
  • Alanine / pharmacology
  • Animals
  • Antiviral Agents / pharmacology*
  • Betacoronavirus
  • COVID-19
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / prevention & control*
  • Disease Models, Animal
  • Lung / pathology
  • Lung / virology
  • Macaca mulatta
  • Male
  • Middle East Respiratory Syndrome Coronavirus / drug effects
  • Middle East Respiratory Syndrome Coronavirus / physiology
  • Pandemics
  • Pneumonia, Viral
  • Post-Exposure Prophylaxis
  • SARS-CoV-2
  • Viral Load
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • remdesivir
  • Adenosine Monophosphate
  • Alanine