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Drugs Used to Fight Hepatitis, Worm Infections Might Stop Zika

A drug already on the market to treat worm infections and another being tested against liver diseases may also help treat Zika virus infections.
Electron microscopy of Zika virus (orange) bound to cell membrane (brown) in neurosphere generated
from human iPS cells.
Electron microscopy of Zika virus (orange) bound to cell membrane (brown) in neurosphere generated from human iPS cells.Credit: Rodrigo Madeiro, PhD - IDOR] / Credit: Rodrigo Madeiro, PhD - IDOR/ Science

A drug already on the market to treat worm infections and another being tested against liver diseases may also help treat Zika virus infections, researchers reported Monday.

The findings are a rare bit of good news about Zika, which has caused epidemics across Latin America and the Caribbean, and smaller outbreaks in Florida, the Pacific and southeast Asia.

Zika has caused smaller epidemics of birth defects, notably brain damage that can cause miscarriages or profound developmental injuries in babies. It can also cause a paralyzing condition called Guillain-Barré syndrome.

It’s spread by mosquitoes and by sex. As of now, there is no vaccine or treatment.

The team at the National Institutes of Health (NIH), Johns Hopkins University and Florida State University looked first in a library of existing drug compounds for products that might act to stop Zika from killing brain cells and perhaps stop it from replicating itself.

“It takes years, if not decades, to develop a new drug."

“It takes years, if not decades, to develop a new drug,” says Hongjun Song of Johns Hopkins, who worked on the project. “In this sort of global health emergency, we don’t have that kind of time.”

But libraries of existing compounds let researchers use a computer to look for drugs that work in specific ways.

“So instead of using new drugs, we chose to screen existing drugs,” said Dr. Guo-li Ming, a neurology professor at Johns Hopkins University School of Medicine. “In this way, we hope to create a therapy much more quickly.”

Related: Who needs to worry about Zika?

They were delighted to find a drug already on the market and considered safe to use in pregnant women. “Niclosamide is an FDA-approved drug (trade name Niclocide) that has been used in humans to treat worm infections for nearly 50 years, and it is well tolerated,” the team wrote in their report, published in the journal Nature Medicine.

“It is known to inhibit several viruses in culture systems, including the Japanese encephalitis flavivirus.”

Japanese encephalitis is a relative of Zika and also carried by mosquitoes.

Tests on human brain stem cells in lab dishes showed it could interfere with Zika’s replication in those cells. “Niclosamide is a category B drug, which indicates that no risk to fetuses has been found in animal studies. It has low toxicity in mammals,” they added.

“Emricasan was well tolerated in human trials, and there were no significant adverse events.”

Another drug, called emricasan, helped prevent Zika from killing those cells.

“Emricasan is currently being evaluated in phase 2 clinical trials for the reduction of hepatic injury and liver fibrosis caused by chronic hepatitis C infection,” the team wrote.

“Emricasan was well tolerated in human trials, and there were no significant adverse events.”

A third compound called PHA-690509 also helped stop Zika replicating and from killing nerve cells, they said.

While the drugs work well in lab dishes full of cells, “we don’t know if they can work in humans in the same way,” Song said.

Related: Could we have a Zika vaccine soon?

Niclosamide works in the gut, but it’s not clear if it’s possible to get it into the brain, Song said.

The researchers think the drugs might work best as a cocktail, attacking the virus from several fronts — in much the same way as drug cocktails fight the human immunodeficiency virus (HIV) that causes AIDS.

“To address these questions, additional studies need to be done in animal models as well as humans to demonstrate their ability to treat Zika infection,” Ming said in a statement. “So we could still be years away from finding a treatment that works.”

The White House has asked for $1.9 billion in federal funding to help pay for studies like these and to keep them going after Zika is no longer making headlines. But Congress could not agree on a funding plan and took a seven-week break without appropriating any cash.

Related: Obama Says Congress Puts Americans at Risk

The NIH, the Centers for Disease Control and Prevention and other agencies have taken money from other programs to pay for urgent Zika research.

At the beginning of the Ebola epidemic in West Africa, researchers complained that they’d been working on drugs and vaccines for years but that inconsistent funding and a lack of interest from Congress and from drug companies made it impossible to make better progress. More than 11,000 people died in Sierra Leone, Liberia and Guinea before the Ebola epidemic wound down last year.