Several drugs already in the pharmaceutical arsenal have potential to fight Zika virus infections, tests with lab-grown human cells reveal.
In the journal Nature Medicine, scientists report screening 6,000 existing compounds already approved for human use or in late-stage clinical trials for other conditions. Several showed the ability to hinder or halt the progress of the mosquito-borne Zika virus in lab-grown human neural cells.
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.”
“It takes years if not decades to develop a new drug,” says Hongjun Song of the Institute of Cell Engineering at the Johns Hopkins School of Medicine. “In this sort of global health emergency, we don’t have that kind of time.”
“So instead of using new drugs, we chose to screen existing drugs,” adds Guo-li Ming, professor of neurology at Johns Hopkins. “In this way, we hope to create a therapy much more quickly.”
Brain cells survive longer
A Zika outbreak began in South America in mid-2015; the disease is now known to be responsible both for microcephaly, in which infants are born with severely underdeveloped brains, and for temporary paralysis in adults due to Guillain-Barre syndrome.
The Zika virus is commonly transmitted from mosquito bites or through sexual contact. Cases transmitted locally by mosquito have occurred in Puerto Rico and, just recently, Florida, and travel-related cases have been identified elsewhere in the United States.
The researchers found earlier this year that Zika targets specialized stem cells that give rise to neurons in the brain’s outer layer, the cortex. In the new study, the team exposed cell cultures to Zika virus and the drugs one at a time, measuring cell death.
Typically, after Zika infection, the damage done to neural cells is “dramatic and irreversible,” says Hengli Tang, professor of biological sciences at Florida State. Some of the compounds tested, however, allowed the cells to survive longer and, in some cases, to fully recover.
The promising drugs are from two classes: neuroprotective drugs, which prevent the activation of mechanisms that cause cell death, and antiviral drugs, which slow or stop viral infection or replication. Three drugs showed results warranting more study: PHA-690509, an investigational compound with antiviral properties; emricasan, now in clinical trials to reduce liver damage from hepatitis C virus and shown to have neuroprotective effects; and niclosamide, a drug already used in humans and livestock to combat parasitic infections. It worked as an antiviral agent in these experiments.
More studies needed
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.”
For example, he says, although niclosamide can safely treat parasites in the human gastrointestinal tract, scientists have not yet determined if it can penetrate the central nervous system of adults or a fetus in the womb to treat the brain cells targeted by Zika.
Nor, he says, do we know if the drugs would address Zika-caused microcephaly or Guillain-Barre.
“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 says. “So we could still be years away from finding a treatment that works.”
The researchers say their next steps include testing the drugs in animal models.
Only one in four Zika-infected people show symptoms, allowing the virus to spread rapidly in areas with local transmission. Many research groups are fast tracking the development of vaccines, treatments, and mosquito control measures to combat further spread.
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. The work had support from the National Institutes of Health, Florida State, Emory, the Brain and Behavior Research Foundation, the New York Stem Cell Foundation, and the Maryland Stem Cell Research Fund.
Source: Johns Hopkins University