Protease inhibitor a potential new avenue for Zika treatment

As of September, the Zika virus was officially on U.S. soil. Local businesses must do everything they can to keep travelers feeling safe, so they remember to come back.
The Sanford Burnham team hopes to develop a "more potent and effective drug" based on a compound that prevented Zika virus infection in humans and mice.

Scientists at Sanford Burnham Prebys have identified a compound that prevents Zika infection by blocking the virus’ protease function. The antiviral, which worked in human cells and mice, could be the basis for a new Zika drug.

Proteases help digest proteins by breaking them down into their component amino acids. But some viruses depend on proteases for replication, making them an attractive target for antiviral drugs. A range of protease inhibitors are already in use to treat HIV and hepatitis C infection, including Merck’s combo drug Zepatier, which was approved last year.

The Sanford Burnham team, led by Alexey Terskikh and Alex Strongin, started off with a library of compounds known to suppress proteases in West Nile Virus, which is in the same family as Zika. They also looked at molecules that are similar in structure to these compounds, according to a press release.

After narrowing the candidates down to three, the team found one that staved off Zika infection in human brain cells and in the blood of mice infected with the virus, according to 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,” Terskikh said in the release.

Terskikh is optimistic about the drug’s safety too. The compound targets a part of the protease that is only present in viruses, so it doesn’t affect human proteases.

The World Health Organization designated the Zika outbreak a global public health emergency in February last year, but pulled the designation in October. While the focus has largely been on a vaccine, Terskikh underscores the need for anti-Zika drugs: "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."

A number of institutions are exploring ways to tamp down on Zika infection. Scientists from Vanderbilt University, Washington University in St. Louis and Integral Molecular produced an antibody that stopped mother-to-fetus transmission of the virus in mice. This could be particularly useful as Zika’s most devastating effects show up in the infants of women who were infected while pregnant. Another team from Washington University used CRISPR to switch off genes in human and insect cells, landing on one that stopped Zika and its related viruses from spreading in the body.