Researchers from the Sanford-Burnham Preby’s Medical Discovery Institute (SBP) in San Diego have pinpointed the molecule that inhibits the Zika virus, a step towards finding a drug to combat the virus, which has become a global epidemic.
“We identified a small molecule that inhibits the Zika virus protease and show that it blocks viral propagation in human cells and in mice,” Alexey Terskikh, Ph.D., associate professor at SBP, said in a statement. “Anti-Zika drugs are desperately needed.
“The fact that the compound seems to work in vivo is really promising, so we plan to use it as a starting point to make an even more potent and effective drug.”
The researchers used a library of compounds that co-author Alex Strongin, Ph.D., professor at SBP, that had previously shown to inhibit the same compound as the West Nile virus. They also tested other structurally similar molecules available at the SBP’s Conrad Prebys Center for Chemical Genomics to determine whether any also blocked the protease.
They were able to identify three promising compounds that were tested for their ability to prevent Zika infection of human brain cells, with the best one also showing the ability to reduce the amount of virus circulating in the blood of Zika-infected mice.
“The inhibitor’s efficacy in animals is the key to the study’s significance,” Terskikh said. “This, and the fact that the compound is likely to be safe make it especially promising.
“The compound blocks a part of the protease that’s unique to viruses, so it doesn’t inhibit similar human proteases. It’s also much more potent than previously identified inhibitors of the Zika protease.”
Zika is a significant emergent threat to global health, particularly during pregnancy. While it is not life-threatening, Zika has severe health implications beyond microcephaly—a condition where an infant’s head is significantly smaller than what is expected.
“Microcephaly is likely just the tip of the iceberg in terms of the potential adverse effects of maternal Zika infection,” Terskikh said. “There may be other, less obvious impacts on brain development that wouldn’t be apparent until later. That’s something we’re also investigating.”
Zika despite not being lethal, Zika is considered a global threat because it is spreading rapidly through the Americas, including through parts of the U.S.
The researchers are also moving forward with an experimental vaccine that is set to move into phase 2 clinical trials in June.
“In addition to a Zika vaccine, we still need antivirals,” Terskikh said. “Some people may be exposed who haven’t been vaccinated.
“Having a way to treat the infection could help stop Zika from spreading and prevent its sometimes devastating effects.”
