Researchers: Treatment for hand, foot and mouth disease may be on horizon

Sept. 22 (UPI) -- Researchers have identified a potential new drug to treat enterovirus 71, a common cause of hand, foot and mouth disease, according to a study published Tuesday in the journal Nature Communications.

The disease typically strikes infants and young children, particularly in Southeast Asia, and no treatment has been approved by the U.S. Food and Drug Administration or its counterparts globally, the researchers said.

The new drug is described as a small molecule that binds to RNA, the virus's genetic material, and changes its 3D shape in a way that stops the virus from multiplying without harming its human host.

"There is currently no specific treatment for hand, foot and mouth disease, nor a widely adopted vaccine, despite the severe neurological complications that can occur in small children," study co-author Amanda E. Hargrove told UPI.

"Other small molecule approaches that target viral proteins have been effective in mice models, but no clinical trials are underway, so we are hoping that this new strategy will open a new door in therapeutic potential," said Hargrove, an associate professor of chemistry at Duke University.

Hand, foot and mouth disease is common globally in children 5 years old and younger, although adults can be infected. In most cases, the symptoms -- mouth sores, skin rash, fever, sore throat and loss of appetite -- are minor, but the disease can lead to severe dehydration and even polio-like paralysis, according to the U.S. Centers for Disease Control and Prevention.

When a virus like enterovirus 71 infects a human cell, it injects its RNA into the cell, hijacking the internal machinery to make copies of itself that eventually burst out to infect neighboring cells.

Earlier research on enterovirus 71 singled out one part of its RNA structure that helps the virus co-opt the host machinery it needs to replicate, researchers said.

This RNA region folds over on itself to form a hairpin, with a bulge in the middle where unpaired nucleotides balloon out to one side, researchers said.

For this study, Hargrove and her colleagues screened a library of some 30 small molecules, looking for those that bind tightly to the bulge and not other sites in the virus's RNA. They identified one molecule, called DMA-135, that enters infected human cells and attaches itself to the surface of the bulge, creating a kink.

This shape change, in turn, opens access to another molecule, a human repressor protein that blocks the "reading out" of the virus's genetic instructions, stopping viral growth in its tracks, the researchers said.

In an experiment, the researchers used the molecule to stop the virus from building up inside human cell cultures in the lab, with bigger effects at higher doses.

It will take at least five years, however, to move any new drug for hand, foot and mouth disease from the lab to medicine cabinets, Hargrove said.

"The first step will be to test the new, related molecules we've designed to see if we can increase antiviral potency while carefully monitoring potential toxicity in human cells," she said.

"Next will come a series of animal studies to test safety and efficacy before ideally moving on to clinical trials."