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Biological Chemistry

Small molecule treatment for Ebola

Prodrug GS-5734 suppresses deadly virus in monkeys

by Bethany Halford
March 21, 2016 | A version of this story appeared in Volume 94, Issue 12

When an Ebola outbreak began ravaging West Africa in 2013, doctors and scientists had few medicines to treat the thousands of people who would become infected with the deadly virus in the years to follow. In fact, no antiviral therapeutics have received regulatory approval or demonstrated clinical efficacy against Ebola to date. There might be new hope, though, thanks to researchers at Gilead Sciences, the U.S. Army Medical Research Institute of Infectious Diseases, the Centers for Disease Control & Prevention, and Boston University. Those scientists, who presented in San Diego, have developed a small molecule called GS-5734 that’s effective at treating monkeys infected with the Ebola virus (Nature 2016, DOI: 10.1038/nature17180). GS-5734 is a monophosphoramidate prodrug of an adenosine analog. Once the small molecule is administered, enzymes in the body cleave GS-5734’s monophosphoramidate and eventually replace it with a triphosphate. This metabolite, the researchers suspect, inhibits the virus’s RNA-dependent RNA polymerase, effectively preventing the virus from replicating by blocking the synthesis of its RNA. Because GS-5734 is also active against other pathogenic RNA viruses in cells, it might find wider medical use, the researchers note. Safety and pharmacokinetic studies are currently ongoing.

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