Frog mucus might seem like the kind of flu remedy a witch doctor would suggest, but in the future, more respected medical professionals could be prescribing it. Researchers at Emory University have found that certain peptides excreted by frogs can fight off human flu strains, and they could be used as emergency stand-ins during flu outbreaks when regular vaccines aren't available.
Made up of short chains of amino acids, peptides are essentially mini-proteins, and they perform a variety of functions in the body. Some peptides are antimicrobial, playing a role in an animal's immune system, and although they generally only benefit the species that's producing them, the Emory team wanted to see if these flu fighters could carry across to humans.
"Different frogs make different peptides, depending on where their habitat is," says Joshy Jacob, co-author of the study. "You and I make host defense peptides ourselves. 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."
For this work, the team collected 32 different peptides from a frog species called Hydrophylax bahuvistara, which is native to southern India. Frogs are a good place to start looking because their peptides are easy to collect and isolate: the researchers simply give them a mild electric shock or rub a powder on their back, and the animals secrete them in defense.
The team tested the peptides against human flu strains, and of the 32 types collected, four of them proved effective. That was a much higher number than the researchers were expecting.
"I was almost knocked off my chair," says 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."
But it's not a good idea to just go out licking frogs the next time you get the sniffles – of those four candidates, it appears only one may be safe for human use. In lab tests, the researchers exposed human red blood cells to the different peptides, and using electron microscopy found that three of them were toxic. The fourth, which the team dubbed "urumin," was lethal to the flu but harmless to us.
The researchers found that urumin was effective against dozens of flu strains. While the exact mechanism isn't clear yet, it appears that the peptide's tactics involve binding to a protein called hemagluttinin on the surface of the virus. Putting the H in H1, this protein is a key part of how the flu virus grips and attacks healthy human cells.
"The virus needs this hemagglutinin to get inside our cells," says Jacob. "What this peptide does is it binds to the hemagglutinin and destabilizes the virus. And then it kills the virus."
When tested on mice, urumin administered through the nose was found to protect the animals from lethal doses of some types of flu, like the H1N1 swine flu that struck in 2009, but had little effect against current strains like H3N2. While the peptides probably won't make for vaccines by themselves, they could be used as stop-gaps where vaccines aren't yet available, to help slow the spread of future pandemics.
The researchers are now developing ways to keep the peptides stable inside the body, where natural enzymes would work to break them down, and continuing to search for frog peptides that might be effective against other viruses.
The research was published in the journal Immunity.
Source: Emory University
