Remdesivir: Experimental Antiviral Drug Shows Promise against MERS Virus in Rhesus Macaques

Middle East respiratory syndrome coronavirus (MERS-CoV) is closely related to the COVID-19 coronavirus (also known as SARS-CoV-2 and 2019-nCoV) that has grown to be a global public health emergency since cases were first detected in Wuhan, China, in December 2019. In a new study, a team of researchers from the National Institute of Allergy and Infectious Diseases (NIAID), Columbia University and Gilead Sciences, Inc. tested the efficacy of the broad-acting antiviral remdesivir in the rhesus macaque model of MERS-CoV infection; the antiviral reduced the severity of disease, virus replication, and damage to the lungs when administered either before or after animals were infected with MERS-CoV. The results appear in the Proceedings of the National Academy of Sciences.

de Wit et al show that remdesivir is a promising antiviral treatment against MERS that could be considered for implementation in clinical trials. This colorized scanning electron micrograph shows MERS virus particles (blue) both budding and attached to the surface of infected VERO E6 cells (yellow). Image credit: NIAID.

de Wit et al show that remdesivir is a promising antiviral treatment against MERS that could be considered for implementation in clinical trials. This colorized scanning electron micrograph shows MERS virus particles (blue) both budding and attached to the surface of infected VERO E6 cells (yellow). Image credit: NIAID.

Remdesivir is a nucleotide prodrug that has broad antiviral activity against viruses from different families in vitro, and therapeutic efficacy in nonhuman primate models of Ebola virus and Nipah virus infections.

Studies in human airway epithelial cells showed that remdesivir also inhibits replication of a wide range of coronaviruses, including MERS-CoV.

With these promising data in mind, NIAID scientist Dr. Emmie de Wit and colleagues tested the prophylactic and therapeutic efficacy of remdesivir treatment in a non-human primate model of MERS-CoV infection, the rhesus macaque.

The study involved three groups of animals: those treated with remdesivir 24 hours before infection with MERS-CoV.

Those treated 12 hours after infection (close to the peak time for MERS-CoV replication in these animals); and untreated control animals.

The authors observed the animals for six days. All control animals showed signs of respiratory disease.

The animals treated before infection fared well: no signs of respiratory disease, significantly lower levels of virus replication in the lungs compared to control animals, and no lung damage.

The animals treated after infection fared significantly better than the control animals: disease was less severe than in control animals, their lungs had lower levels of virus than the control animals, and the damage to the lungs was less severe.

“Our data show that remdesivir is a promising antiviral treatment against MERS that could be considered for implementation in clinical trials,” said Dr. de Wit and colleagues.

“It may also have utility for related coronaviruses such as the novel coronavirus COVID-19 emerging from Wuhan, China.”

Several clinical trials of remdesivir for COVID-19 are under way in China, and other patients with COVID-19 have received the drug under a compassionate use protocol.

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Emmie de Wit et al. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. PNAS, published online February 13, 2020; doi: 10.1073/pnas.1922083117

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