Washington: A new compound that blocks the Ebola virus' ability to replicate has been found to provide full protection to monkeys when treated three days after the deadly infection, scientists say.
The initial work identified the precursor to GS-5734, a small-molecule antiviral agent, which led the researchers to further refine, develop and evaluate the compound.
Led by US Army Medical Research Institute of Infectious Diseases (USAMRIID) Science Director Sina Bavari, 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 per cent 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.
"The compound, which is a novel nucleotide analog prodrug, works by blocking the viral RNA replication process," said Travis Warren, a principal investigator at USAMRIID.
"If the virus can't make copies of itself, the body's immune system has time to take over and fight off the infection," Warren said.
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 said.
"In addition to 100 per cent survival in treated animals, the profound suppression of viral replication greatly reduced the severe clinical signs of disease," he said.
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, Bavari said.
Ebola virus causes severe hemorrhagic fever in humans and nonhuman primates with high mortality rates and continues to emerge in new geographic locations, including West Africa, the site of the largest outbreak to date.
