Scientists report that a specialized drug screen test using lab-grown human cells has revealed two classes of compounds already in the pharmaceutical arsenal that may work against mosquito-borne Zika virus infections.
Zika has caused smaller epidemics of birth defects across Latin America and the Caribbean, and smaller outbreaks in Florida, the Pacific and Southeast Asia. These can notably damage the brain and cause miscarriages or profound developmental injuries in babies. It can also cause a paralyzing condition called Guillain-Barré syndrome.
It's spread by mosquitoes and by sex. As of now, there is no vaccine or treatment.
A team of researchers from Florida State University, Johns Hopkins University and the National Institutes of Health has found existing drug compounds that can both stop Zika from replicating in the body and from damaging the crucial fetal brain cells that lead to birth defects in newborns.
Hongjun Song, PhD, study coauthor who directs the stem cell program in the Institute of Cell Engineering at Johns Hopkins, said in a press release from the university, "It takes years, if not decades, to develop a new drug. In this sort of global health emergency we don't have that kind of time."
The team tested the drugs against three strains of Zika virus: African, Asian, and Puerto Rican. The screening method also used a type of protein that causes cell death when infected with the virus. Screening 6,000 compounds yielded more than 100 that showed promise. The investigators then tested those on brain cells that had been infected with Zika virus to see if any offered protection. The three lead compounds they found either inhibited Zika replication or prevented the virus from killing brain cells.
The new findings are an extension of previous work by the research team, which found that Zika mainly targets specialized stem cells that give rise to neurons in the brain's outer layer, the cortex. The researchers observed Zika's effects in two- and three-dimensional cell cultures called "mini-brains," which share structures with the human brain and allow researchers to study the effects of Zika in a more accurate model for human infection.
In the current study, the research team exposed similar cell cultures to the Zika virus and the drugs one at a time, measuring for indicators of cell death, including caspase-3 activity, a chemical marker of cell death, and ATP, a molecule whose presence is indicative of cell vitality.
Typically, after Zika infection, the damage done to neural cells is "dramatic and irreversible," says Hengli Tang, Ph.D., professor of biological sciences at Florida State University. However, some of the compounds tested allowed the cells to survive longer and, in some cases, fully recover from infections.
The scientists said the next step is to see if vertical transmission among mosquitoes occurs in nature. Passage of the virus to mosquito offspring has been shown for other diseases such as dengue and yellow fever. They add that vertical transmission seems to provide a way for viruses to survive adverse conditions such as cold, hot, and dry weather, and even population immunity.
To assess the natural process, the investigators will need to collect Aedes larvae from water in abandoned tires and other places in areas where Zika virus is circulating.