Rhesus monkeys were completely protected from the deadly Ebola virus when treated three days after infection with a compound that blocks the virus's ability to replicate. These encouraging preclinical results suggest the compound, known as GS-5734, should be further developed as a potential treatment, according to research findings to be presented at the IDWeek conference.
The initial work identified the precursor to GS-5734, a small-molecule antiviral agent, which led to the effort by Gilead and USAMRIID to further refine, develop and evaluate the compound. Led by USAMRIID Science Director Sina Bavari, Ph.D., the research team used cell culture and animal models to assess the compound's efficacy against several pathogens, including Ebola virus.
In animal studies, treatment initiated on day 3 post-infection with Ebola virus resulted in 100 percent survival of the monkeys. They also exhibited a substantial reduction in viral load and a marked decrease in the physical signs of disease, including internal bleeding and tissue damage.
In cell culture studies, GS-5734 was active against a broad spectrum of viral pathogens. These included Lassa virus, Middle East Respiratory Syndrome (MERS) virus, Marburg virus, and multiple variants of Ebola virus, including the Makona strain causing the most recent outbreak in West Africa.
"This is the first example of a small molecule - which can be easily prepared and made on a large scale - that shows substantive post-exposure protection against Ebola virus in nonhuman primates," Bavari commented. "In addition to 100 percent survival in treated animals, the profound suppression of viral replication greatly reduced the severe clinical signs of disease."
Taken together, the robust therapeutic efficacy observed in primates and the potential for broad-spectrum antiviral activity suggest that further development of GS-5734 for the treatment of Ebola virus and other viral infections is warranted.
Gilead Sciences is currently conducting phase I clinical studies of the compound in healthy human volunteers to establish the safety and pharmacokinetic profile.
Material originally posted by US Army Medical Research Institute of Infectious Diseases.