Frog Mucus Yields Virus-Killing Peptides

Researchers have isolated a peptide from frog mucus that can kill a wide range of flu viruses but appears harmless to human cells.

AsianScientist (Apr. 28, 2017) – The slime from a colorful, tennis-ball-sized frog (em>Hydrophylax bahuvistara) from southern India has been found to destroy many strains of human flu and protect mice against flu infection, according to a study published in Immunity.

The slime contains a peptide that seems to work by binding to a protein that is identical across many influenza strains. In lab experiments, it was able to neutralize dozens of flu strains, from the 1934 archival viruses up to modern ones. The researchers named the newly identified peptide urumin, after the urumi, a sword with a flexible blade that snaps and bends like a whip, which comes from Kerala, just like the frog itself.

“Different frogs make different peptides, depending on where their habitat is. You and I make host defense peptides ourselves,” said flu specialist and study co-author Joshy Jacob, an associate professor at Emory University. “It’s a natural innate immune mediator that all living organisms maintain. We just happened to find one that the frog makes that just happens to be effective against the H1 influenza type.”

Practically all animals make at least a few anti-microbial host defense peptides as part of their innate immune systems, and researchers are only beginning to catalog them. However, frogs have drawn the most attention as a source of host defense peptides, because it’s relatively easy to isolate the peptides from their mucus. Researchers can simply give the frogs a small electric shock or rub a powder on the frogs to make them secrete their defense peptides, which can then be collected.

Researchers from the Rajiv Gandhi Center for Biotechnology in Kerala, India, have been isolating peptides from local frogs and screening them for potential anti-bacterials, but Jacob wondered if there might also be peptides that neutralize human-infecting viruses. Jacob and his colleagues screened 32 frog defense peptides against an influenza strain and found that four of them had flu-busting abilities.

“I was almost knocked off my chair,” said Jacob. “In the beginning, I thought that when you do drug discovery, you have to go through thousands of drug candidates, even a million, before you get one or two hits. And here we did 32 peptides, and we had four hits.”

Unfortunately, when the researchers exposed isolated human red blood cells (in a dish) to the flu-buster peptides, three out of the four proved toxic. However, the fourth—urumin—seemed harmless to human cells but lethal to a wide range of flu viruses. Electron microscope images of the virus after exposure to urumin reveal a virus that has been completely dismantled.

Jacob’s team is still working out the details of the flu-destroying mechanism, but the urumin appears to work by targeting a viral surface protein called hemagluttinin, the H in H1N1.

“The virus needs this hemagglutinin to get inside our cells,” said Jacob. “What this peptide does is it binds to the hemagglutinin and destabilizes the virus. And then it kills the virus.”

The article can be found at: Holthausen et al. (2017) An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Viruses.


Source: Cell Press; Photo: Sanil George & Jessica Shartouny.
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