Remdesivir Shows Promise Against Nipah Virus in Monkeys
The experimental drug protected 4 African green monkeys following a lethal dose of Nipah virus in a study conducted by NIAID, CDC, and Gilead investigators.
Remdesivir (GS-5734) is a nucleotide analog prodrug that is being developed by Gilead Sciences, Inc., to protect against pathogenic infections such as Ebola. The antiviral has broad-spectrum antiviral activity that was shown to inhibit filovirus, coronavirus, and paramyxovirus replication and is currently being used in the Ebola outbreak in the North Kivu province of the Democratic Republic of the Congo.
But now, the National Institutes of Health (NIH) has announced that the experimental antiviral completely protected 4 African green monkeys from Nipah virus in a recent study.
Nipah virus was discovered in 1999 in Malaysia and is an emerging pathogen that is isolated primarily in Bangladesh and India. It is spread by fruit bats, however, person-to-person transmission is possible. The virus can cause neurological and respiratory disease and delayed relapse can result in brain inflammation or encephalitis. Overall, the virus has a mortality rate of about 70%. In a recent outbreak in May 2018, 23 cases were detected in India, resulting in 21 deaths—a case fatality rate of about 91%.
The findings of the study were published in a report in Science Translational Medicine.
The study concept was a collaboration between investigators with the US Centers for Disease Control and Prevention (CDC) and the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. The study was then conducted by Gilead and NIAID with laboratory serology and pathology support from the CDC.
For the study, 2 groups of 4 African green monkeys each were first inoculated intranasally and intratracheally with a lethal dose of Nipah virus Bangladesh. The 4 monkeys in the treatment group then received a dose of intravenous (IV) remdesivir 24 hours after infection and then a daily IV dose for a total of 12 consecutive days following.
In total, the NIAID team observed the animals for 92 days after infection, taking 14 clinical samples during the time period. This long period of observation granted the investigators time to monitor the central nervous system for evidence of disease, which can be slow to develop when caused by Nipah virus.
According to investigators, 2 treated animals developed signs of mild respiratory disease, which resolved within 3 weeks and the other 2 treated animals showed no sign of illness. All 4 of the remdesivir-treated monkeys remained healthy for the remainder of the study.
The 4 monkeys who were not treated with remdesivir began showing signs of illness within 4 days of infection and rapidly developed fatal disease within 8 days.
Remdesivir is the second experimental treatment, after monoclonal antibody m102.4, shown to prevent severe Nipah virus disease in a monkey model when administered following inoculation.
“…Our findings strongly support using remdesivir in response to the next Nipah virus outbreak, either under compassionate use protocol or possible a randomized clinical trial protocol,” the authors write in their report.
Remdesivir was permitted for treatment under compassionate use protocol in the ongoing Ebola outbreak in the Democratic Republic of the Congo until November when a randomized controlled trial was launched in the outbreak zone. The antiviral is also being studied in a phase 2 clinical trial for treatment of male Ebola virus disease survivors with persistent viral RNA in their semen.