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Drug Development

Antiviral provides postexposure protection against ebolavirus in monkeys

Study of possible prodrug showed it protected monkeys exposed to Sudan ebolavirus

by Sarah Braner
March 18, 2024


A research team has found that obeldesivir, a prodrug candidate similar to the antiviral remdesivir, had a strong postexposure prophylactic effect in nonhuman primates against the species known as Sudan ebolavirus. Obeldesivir is an oral antiviral developed by Gilead Sciences that is eventually converted to an active adenosine triphosphate analogue, which inhibits the RNA polymerase enzyme of a RNA-dependent target virus.

A structure of obeldesivir.

Publishing the results in Science (2024, DOI: 10.1126/science.adk6176), a study by Thomas Geisbert’s lab showed that the compound decreased concentrations of three filoviruses—Marburg virus and the Zaire and Sudan ebolavirus strains—in vitro. Following this initial trial, they then, five cynomolgus monkeys were injected with a lethal dose of Sudan ebolavirus; 24 h later, they were given their first dose of obeldesivir. The monkeys were treated for 10 days with obeldesivir; all five survived and showed no obvious signs of disease, according to the researchers. Separately, the team injected another five monkeys with the same dose of Sudan ebolavirus but gave them obeldesivir for 5 days postexposure; three survived.

There are few options for protecting a person from ebola disease after they’ve been exposed. Currently available vaccines for ebolaviruses don’t work on every strain, and monoclonal antibodies—which are in short supply to begin with—have to be administered through an IV, which makes it difficult to respond quickly, Geisbert tells C&EN. But a series of pills would be much easier to administer and much less expensive, thus allowing for a much faster response.

“That’s a game changer,” Geisbert says.

Armand Sprecher, an emergency physician who has worked with Doctors Without Borders and who wrote an accompanying commentary for the study, says that a prophylactic, in addition to reducing deaths, could help outbreak responders develop a better relationship with the people in affected communities.

“If you can offer them some hope, then they will stay engaged with you,” he tells C&EN.



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