Hopkins researchers test Zika therapies

Although the first case of Zika was recorded in 1947, the virus only developed public and scientific interest many years later in 2015 when a pandemic outbreak began in South America. The outbreak spread to multiple regions worldwide. The disease is primarily spread through travelers who have been bitten by mosquitoes contamined by the virus and sexual contact between infected and uninfected people.

A total of 2,260 reported cases of Zika have been documented in the continental United States. In Puerto Rico, a total of 7,855 locally transmitted cases have been reported. In March, researchers at Hopkins, Florida State University and Emory University shed light on the primary concern of Zika, which is its ability to cause microcephaly, a severe birth defect that prevents the full development of an infant’s brain.

In the present study, rather than trying to develop a new drug to tackle Zika, scientists are collaborating to conduct a screening of 6,000 existing drugs to discover if one of them may be an effective Zika therapy. All of these drugs have already been approved for human use by the U.S. Food and Drug Administration or are in late-stage clinical trials.

“It takes years if not decades to develop a new drug,” Hongjun Song, director of the Stem Cell Program in the Institute of Cell Engineering at Hopkins, told The Hub. “In this sort of global health emergency, we don’t have that kind of time.”

“So instead of using new drugs, we chose to screen existing drugs,” Guo-li Ming, a professor of neurology at the School of Medicine, said according to The Hub. “In this way, we hope to create a therapy much more quickly.”

Earlier this year, the team of researchers discovered that Zika targets neural progenitor stems that eventually develop into neurons comprising the cortex cells in the brains of infants. The team was able to observe Zika’s effects in “mini-brains”, or 2D and 3D cell cultures that are composed of cells similar to those in the brain during embryonic development. These “mini-brains” provided scientists with a realistic model of the human brain to study human infection.

The researchers exposed these 3D cell cultures, called organoids, to Zika and different drugs one at a time. They looked for specific markers of cell death, like caspase 3 activity and ATP, a molecule that catalyzes cell vitality. After cells are infected with Zika, the damage is usually significant and irreversible. A few particular drugs tested in the Zika-infected cells allowed the cells to survive longer and in some cases to fully recover.

Overall the scientists found three particular drugs that could potentially be developed into an anti-Zika therapy: PHA-690509, a compound with antiviral properties, Emricasan, a drug that is now in clinical trials to reduce damage to the liver in Hepatitis C and Niclosamide, a drug already used in humans and livestock to combat parasitic infections.

Though these drugs warrant further research and attention, Song cautioned that while these drugs are effective in combating Zika in cells, their effects on treating Zika in humans could be different. Additionally, the researchers are unsure of how these drugs would combat other aspects of Zika in adults, like the paralysis induced from Guillain-Barré Syndrome. The researchers now plan to test these drugs in animal models to get a better picture of their efficacy in vivo.