New hope for Zika treatment found in large-scale screen of existing drugs

Prof Tang and his colleagues identified two different groups of compounds that could potentially be used to treat Zika – one that stops the virus from replicating, and the other that stops the virus from killing foetal brain cells, also called neuroprogenitor cells.

Additional authors of the study are from the National Institutes of Health, Icahn School of Medicine at Mount Sinai, Zhejiang University in China, Emory University, Florida State, and Johns Hopkins.

In addition to NCATS, FSU and JHU, the research was supported by Emory University, Atlanta; the Maryland Stem Cell Research Fund, Columbia; NIH’s National Institute of Neurological Disorders and Stroke through grants NS048271 and NS095348, NS047344 and NS097206; and NIH’s National Institute of Allergy and Infectious Diseases through grant AI119530.

In a paper published Monday in the journal Nature Medicine, researchers presented their findings of 6,000 screenings of existing compounds now in late-stage clinical trials or already approved for human use for other conditions.

“It takes years if not decades to develop a new drug”, said the study’s co-author Hongjun Song, who specializes in degenerative neurodegenerative diseases at Johns Hopkins School of Medicine, in a statement. “In this sort of global health emergency, we don’t have that kind of time”.

“The idea was to identify drugs that are already out there that could be moved more quickly into clinical studies with people with Zika infections”, said Shelton Bradrick, a co-author of the study. The screening method also used a type of protein that causes cell death when infected with the virus. JHU is working on a mouse model to study the neuroprotective effects of the compounds identified from the screen and studying the mechanism of action of the lead compounds. Zika is so devastating that the damage it does has been thought to be irreversible. This outbreak is now known to be responsible for an increase in cases of microcephaly – a severe birth defect in which afflicted infants are born with underdeveloped brains.

Emiracsan is in clinical trials for use in preventing liver damage from hepatitis C infection. The compounds include emricasan, an investigational drug now being evaluated in a clinical trial to reduce liver injury and fibrosis, and niclosamide, a U. S. Food and Drug Administration-approved drug for use in humans to treat worm infections.

Song cautions that the three drugs “are very effective against Zika in the [laboratory] dish, but we don’t know if they can work in humans in the same way”.

Nor, he says, do they know if the drugs would address the wide range of effects of Zika infection, which include microcephaly in fetuses and temporary paralysis from Guillain-Barre syndrome in adults.

“So instead of using new drugs, we chose to screen existing drugs”, adds Guo-li Ming, professor of neurology at Johns Hopkins.

Only one in four Zika-infected people show symptoms, allowing the virus to spread rapidly in areas with local transmission. Nature Medicine. August 29, 2016.

To gauge Zika transmissibility to mosquito offspring, researchers experimentally infected the mosquitos in the lab and collected and incubated the eggs. The team’s next step will likely be testing the efficacy of these drugs in animal models to see if they have the ability to combat Zika in a living organism.

They could also wear long sleeves and long trousers – especially during daylight, when the mosquitoes tend to be most active, health officials say.

They are aggressive feeders, commonly biting multiple people in quick succession, fueling the spread of the virus. Spraying affects adults, but it does not usually kill the immature forms-the eggs and larvae.

The scientists said the next step is to see if vertical transmission among mosquitoes occurs in nature.

The Zika (ZEE’-ka) virus was first discovered in monkey in Uganda in 1947 – its name comes from the Zika forest where it was first discovered.