Wednesday, August 31, 2016

A new screening method for Zika virus inhibition shows that existing compounds may be useful

This image shows Zika virus infection in a region of cell death in human forebrain organoids. Credit: Xuyu Qian, Johns Hopkins University via ScienceDaily
Here's some good news in the fight against Zika. Researchers recently screened 6,000 already existing drugs, clinical candidates, and pharmacologically active compounds against Zika infection in monolayer cell culture and organoids, finding three categories of compounds that are promising. The researchers first screened the compounds using 1,536-well plates to identify promising compounds that were later screened in organoids. 

Because Zika specifically targets neural stem cells, researchers sought to disrupt that interaction. The three compound categories have various targets that either target the virus directly or the suppress the 
infection-induced caspase-3 activity (a general response to many infections that many pathogens, such as Influenza A virus, need to replicate efficiently). This caspase-3 activity leads to programmed cell death (also known as apoptosis) and is the hallmark of many viral infections. One pan-capase inhibitor reduced the damage to progenitor cells in monolayer cell culture and organoids. Other compounds that inhibited cyclin-dependent kinases directly impacted Zika virus and reduced replication in this screening system. The third compound category contained niclosamide, a category B anthelmintic drug that is already FDA approved, which also inhibited Zika virus replication. Niclosamide is currently used to treat people that have tapeworms. Although each compound category worked on their own, when a compound from each category was used together, the neural progenitor cells had more protection suggesting that a combination therapy might be the best option.
The researchers do offer a word of caution. These compounds have only been tested in cell culture at this point and more work is needed to see if they work in humans. But this is an exciting study as the researchers have developed an efficient system to screen compounds for activity against Zika virus. Other existing compounds could be screened this way, as well as any newly discovered compounds.