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Researchers Identify Strong Drug Candidate for Treatment of Zika Virus

JUL 27, 2017 | BRIAN P. DUNLEAVY
*Updated on 7/27/2017 at 1:50 PM EST

Mosquito season is underway in the southern United States, but it is a year-round proposition in certain regions of South America and the Caribbean.

Which is why the lack of an effective treatment for Zika virus infection, the mosquito-borne disease that has plagued Brazil since 2014 and Puerto Rico since 2016—and even appeared in Florida and Texas last summer—remains a confounding clinical challenge. This is despite the fact that the epidemic has, at least in the southern hemisphere, seemingly ended, due at least in part to “herd immunity,” according to experts.

However, recent research performed at Weill Cornell Medicine/Memorial Sloan Kettering and published in the journal Cell Stem Cell suggests that a possible cure may be hiding in plain sight.

For the study, the research team—made up of surgeons, neuroscientists, pharmacologists, and biochemists, among other specialists—screened the Prestwick Library of drug compounds, which includes more than 1,100 medications approved by the US Food and Drug Administration and candidate products, with known bioavailability and safety in humans. They treated human pluripotent stem cell (hPSC)-derived human cortical neural progenitor cells (hNPCs) with each drug for 1 hour before exposing them to Zika virus (MR766 strain) for 2 hours. After culturing the cells for 3 days, the team stained them with antibodies against the Zika envelope protein (ZIKV E) and a cell proliferation marker (Ki67) and then performed quantifications using an automated imaging and analysis system. Compounds that increased total cell number by >100% and suppressed the virus to <20% of controls were considered “positive hits.”

In the end, they identified 9 compounds that significantly inhibit Zika, without inhibiting cell proliferation at 10 μM, and selected the 2 that showed the highest efficacy—the sedative hippeastrine hydrobromide (HH) and the blood pressure medication amodiaquine dihydrochloride dihydrate (AQ)—for further analysis. They found that both effectively inhibited Zika virus infection and “blocked [Zika]-induced growth arrest or apoptosis compared with controls. The drugs also “significantly suppressed the production of viral RNA. Furthermore, transcript profiling revealed that both HH and AQ reversed the “transcriptional changes induced by” Zika, and that treatment of the test cells with 25 μM of HH or 15 μM of AQ “effectively inhibited infection of another [Zika] strain, PRVABC59.”



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