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 way stops the virus replicating in the body, and the other way stops the virus activity in fetal brain cells that leads to birth defects in newborns.
Although first identified in monkeys and then humans in Africa just after World War II, it is only recently that we have learned Zika virus can cause birth defects such as microcephaly and Guillain-Barré syndrome in humans.
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
- Zika virus primarily transmits to humans via the bite of an infected Aedes mosquito
- Sexual transmission is also possible, and
other modesare also under investigation
- Zika virus infection can only be confirmed through lab tests on body fluids, such as blood, urine, saliva, or semen.
The team 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 class of compounds 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 – the researchers found they increased protection of precursor cells from cell death induced by the Zika virus.
The researchers are continuing to work on the compounds and hope to start testing them on animal models of Zika infection soon.
“It takes years if not decades to develop a new drug. In this sort of global health emergency, we don’t have time. So instead of using new drugs, we chose to screen existing drugs. In this way, we hope to create a therapy much more quickly.”
Prof. Hongjun Song, Johns Hopkins University School of Medicine, Baltimore, MD
In the United States, there have been 584 cases of pregnant women infected with Zika, mostly as a result of traveling to areas where there is mosquito transmission. So far, 42 cases of locally transmitted Zika virus infection have been identified in Florida.
In the following video from FSU, Prof. Tang and colleagues describe their work and their hope that it will lead to effective anti-Zika treatments: