After screening thousands of drugs already approved or undergoing clinical trials, researchers have identified two groups of compounds that can treat Zika virus infections in two ways: one stops the virus replicating in the body, and the other stops the virus activity in fetal brain cells that leads to birth defects in newborns.
The new study, published in Nature Medicine, is a breakthrough because it means effective treatments for Zika could be just around the corner, without having to wait the many years it normally takes to develop a new drug from scratch.
Hengli Tang, a professor of biological science at Florida State University (FSU) in Tallahassee and one of the senior investigators on the study, explains:
“We focused on compounds that have the shortest path to clinical use. This is a first step toward a therapeutic that can stop transmission of this disease.”
One of the compounds he and his colleagues discovered is the basis for a drug called Niclosamide that is approved by the Food and Drug Administration (FDA). The drug is commonly used to treat tapeworm and animal studies show it is safe for use in pregnancy.
In theory, doctors could prescribe the drug today, but it needs to undergo tests to repurpose it as a treatment for Zika virus infection.
Earlier this year, members of the team had found a link between Zika and microcephaly - a severe birth defect where babies are born with a much smaller head and brain. This led to the search for drug compounds that might prevent the viral damage.
For their new work, the team developed a drug repurposing screen, a relatively new method that researchers are using to speed up drug development. They screened 6,000 compounds that were either already approved by the FDA or were undergoing clinical trials. In either case, the route to finding a successful candidate for Zika treatments would be considerably shorter than developing a new drug from scratch. The two classes of compounds they identified are capable of protecting brain cells from cell death induced by Zika virus activity.
One class of compounds is antiviral in nature and stops the virus multiplying.
The other is neuroprotective in nature and stops the virus carrying out cell-damaging “caspase-3 activity” in human cortical neural progenitors - precursors to brain cells in fetal development.
When they tested combination treatments using one compound from each category - antiviral and neuroprotective - researchers found they increased protection of precursor cells from cell death induced by the Zika virus.
Researchers are continuing to work on the compounds and hope to start testing them on animal models of Zika infection soon.
