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Why the next flu medicine could come from frog mucus

What’s more amazing than kissing a frog and getting a handsome prince? How about scraping off a bit of the mucus layer that covers his skin and finding in it a potent weapon against influenza?

That, quite simply, is what scientists from Emory University appear to have done in discovering an antimicrobial peptide on the skin of Hydrophylax bahuvistara, a species of frog native to southern India. What they found could treat a relentless scourge of humankind that kills as many as half a million people around the world each year.

There, in the film of secretions that protects the frog’s skin from deadly pathogens, scientists have identified a string of amino acids that completely destroys a wide swath of influenza A viruses while doing no harm to healthy human red blood cells.

This discovery, reported Tuesday in the journal Immunity, will face many hurdles before it can become an actual influenza treatment. But its novelty is a potential source of strength against flu viruses that have begun to develop resistance to existing antiviral medications.

Each strain of the flu is named for its particular combination of two surface proteins, hemagglutinin (of which there are 18 known varieties) and neuraminidase (of which there are 11). The most common form of seasonal influenza has the H1 version of hemagglutinin (along with the N1 version of neuraminidase); in laboratory experiments, the frog peptide wiped out every type of H1 flu that was tested.

The current version of H1N1 flu came on the scene in 2009 with the H1N1 “swine flu” pandemic that combined viruses from pigs, birds and people. When the virus first emerged, humans had limited immunity against it, but public health measures and good luck conspired to protect us from disaster. Scientists fear that, in the absence of a wide-spectrum weapon against flu, we won’t be so lucky next time a new strain appears.

There’s no shape-shifting prince in this story, but there is a sword: the Emory team has dubbed the virus-killing peptide “urumin.”

That moniker is derived from the word urumi, the deadly three-pronged ribbon sword used by skilled practitioners of Kerala Kalari Payat, sometimes called the “mother of all martial arts.” Kalari warriors, who would wear this fearsome weapon around their waists, originated from the same province in Southern India that is the native habitat of Hydrophylax bahuvistara.

The discovery is a reminder of the value of preserving biodiversity as a source of inspiration for new human drugs.

To protect themselves in a soup of potentially dangerous microbes, many plants and animals — including frogs — coat themselves with “host defense peptides.” Those peptides have led to the discovery of many antibiotic agents, which is why researchers from the Rajiv Gandhi Center for Biotechnology in Kerala, India, have been swabbing the skins of local frogs and screening these samples.

The study’s lead author, Emory flu expert Joshy Jacob, wondered if the frog mucus might also contain peptides that could neutralize viruses that attack humans. In what is normally an exhaustive process of sifting, Jacob and his team started by screening 32 peptides against a strain of influenza.

To his astonishment, the team immediately found four peptides that attacked influenza. Urumin was the only one that did so without inflicting collateral damage on healthy human cells.

After isolating urumin, the researchers sequenced the genome of their find. Then they chemically synthesized it. Testing this agent in human blood samples infected with influenza A virus, they found that it seemed to home in on the hemagglutinin protein.

"What this peptide does is it binds to the hemagglutinin and destabilizes the virus,” Jacob said. ”And then it kills the virus."

By targeting a protein that is common across many different flu strains, the frog peptide behaved like a universal flu vaccine. Indeed, urumin neutralized dozens of flu strains, ranging from viruses that circulated in 1934 right up to modern ones.

It was also effective at destroying H1 influenza A viruses that had developed resistance to antiviral medications. Current drugs used to blunt the attack of many flu viruses target the neuraminidase protein. But these drugs — including zanamivir, oseltamivir, peramivir and laninamivir — are quickly thwarted when neuraminidase mutates.

Urumin was not so easily put off because it focused on the hemagglutinin protein instead.

Having effective antiviral medications is especially important when a flu strain emerges before a vaccine can be formulated to protect against it. In these cases, giving drugs to people after they’re infected can make infections milder and shorten the time an infected person is sick. It may even make the virus less likely to spread to others.

For Jacob and his team, the next step will be to test urumin in animals of increasing complexity, even as they deepen their understanding of exactly how it works.

melissa.healy@latimes.com

@LATMelissaHealy

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A previous version of this story incorrectly referred to frogs as invertebrates.
Copyright © 2017, Los Angeles Times
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