A new small-molecule drug was recently shown to protect Rhesus monkeys from the Ebola virus, decreasing viral loads significantly and resulting in 100% survival of the monkeys. This compound was also shown to successfully treat 2 human Ebola patients for whom the drug was given for compassionate use. These results make the compound GS-5734 a likely pharmaceutical candidate for Ebola treatment.
Ebola infection and transmission caused a huge international health crisis in 2015 in West Africa, the site of the largest outbreak in history. The virus causes severe hemorrhagic fevers that lead to high mortality rates, since there are no licensed vaccines or therapies against this virus. While the outbreak is currently under control, there’s no guarantee that such event won’t be repeated. As such, research into possible Ebola treatment is imperative.
The small-molecule compound is described as a nucleotide analog prodrug, inhibiting the incorporation of the adenosine base in the viral DNA. This effectively “blocks the virus's ability to replicate its own genetic material,” said first study author, Travis Warren. "With this process inhibited, the virus can't make copies of itself. Additionally, we saw no evidence from genetic sequence analyses that the virus was able to generate resistance to GS-5734," he added.
In Rhesus monkeys treated with the GS-5734 compound within 3 days after infection, the researchers noticed remission of physical Ebola symptoms and decreased viral load count. Remarkably, these treated monkeys showed 100% survival after infection, showing promising evidence of the efficacy of this drug.
GS-5734 has also shown to be effective in cells grown on laboratory dishes. In these systems, the compound was active against a broad spectrum of viral pathogens, including multiple strains of the Ebola virus, as well as Middle East Respiratory Syndrome (MERS) virus, and Marburg virus. These additional results could extend the application of the compound to treating multiple other viral-associated diseases.
"GS-5734 has several favorable characteristics for potential treatment of Ebola virus disease in humans. It is made using well-controlled chemical synthesis procedures, is stable, and can be made on a large scale," said Sina Bavari, senior study author. "It shows substantive post-exposure protection against Ebola virus in nonhuman primates, even when treatments were started after virus had spread to the blood in some animals."
The research team is excited at the prospects of conducting further testing on this compound. Already, Gilead Sciences, a prominent collaborator in this study, is conducting a phase I clinical trial with GS-5734 to determine safety and pharmacokinetic properties in healthy human patients.
In two instances where the compound was given to patients for compassionate use, both patients recovered fully and were discharged from the hospitals. How GS-5734 played a role in the recovery will be extensively studied in the future.
Additional source: Nature journal, Science Daily