Animals

Frog Mucus Compound Kills Many Strains of the Human Flu

A molecule found in frog mucus could lead to future drugs that may both treat and prevent illness resulting from various strains of the H1 influenza virus.

The frog Hydrophylax bahuvistara, which produces a flu-fighting compound found in mucus on its skin. | Sanil George and Jessica Shartouny
The frog Hydrophylax bahuvistara, which produces a flu-fighting compound found in mucus on its skin. | Sanil George and Jessica Shartouny

Before refrigeration, many people from Russia and Finland used to follow an old practice of putting a frog into a bucket of milk in order to prevent the liquid from going sour. The unusual technique often worked, because frog skin is covered with a slimy mucus that can kill many different species of bacteria and viruses. (The milk preservation method is not something to try today, however, both for the sake of the frog and for the dairy consumer.)

Today, researchers announce that they have just discovered that a colorful tennis-ball sized frog from India produces a compound in its skin mucus that can neutralize numerous strains of H1 flu viruses, which are known to infect humans and other animals. As a result, the compound — a host defense peptide described in the journal Immunity — could lead to a future powerful influenza vaccine and/or drug treatment.

“In the past when you did drug discovery, you might have to investigate thousands or even millions of candidates to find one or two peptides that can neutralize viruses affecting humans,” senior author Joshy Jacob, an associate professor at Emory University’s Emory Vaccine Center, told Seeker. “In this case, we screened 32 peptides from the frog and had four hits. I was very surprised and was almost knocked off my chair!”

Out of the four frog peptides found to neutralize viruses that can infect humans, three proved to be toxic to our species. The scientists made this determination after exposing isolated human red blood cells in a dish to the compounds.

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The fourth appears to be safe for human use. Electron microscopy indicates that this defense peptide disrupts the integrity of the H1 flu virus while leaving overall cells intact. It achieves this feat by binding to the stalk of hemagglutinin, a less variable region of the flu virus that has been the focus of other research groups trying to develop a universal influenza vaccine.

The researchers named the flu-fighting peptide “urumin” after the urumi, which is a sword with a flexible blade that snaps and bends like a whip. The weapon comes from the same Indian province, Kerala, as the frog.

Jacob said that frogs are not somehow more antimicrobial than the rest of us. All animals, including humans, produce defense peptides to keep bacteria and viruses in check.

“It’s just that it is easier to collect the peptides from the mucus on frog skin,” he said, mentioning that giving the frogs very small electrical shocks or rubbing a powder on their skin can cause them to secrete their peptide-rich slime.

A side-by-side electron microscope image of a flu virus before (left) and after (right) being exposed to urumin, a virus-fighting compound found in frog mucus. | David Holthausen

All frogs produce different defense peptides. In this case, the frog (Hydrophylax bahuvistara) happens to produce one that works against H1. Flu viruses from humans cannot infect frogs, so the orange and dark brown amphibian likely evolved urumin to fight off some other pathogen.

To investigate how well urumin might help mammals, the researchers placed some of it inside the noses of unvaccinated mice. They then exposed the mice to flu viruses. The peptide neutralized all H1 strains, including those going back to 1930. It was not, however, effective against other known influenza viruses, such as H3N2.

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Jacob and his team are now attempting to stabilize urumin and other potentially beneficial peptides, which can easily be broken down by enzymes in the body. He estimates that it could take about a decade before any possible related treatment is ready and approved for human use.

The researchers are now also seeking frog-derived peptides that might neutralize viruses like those that cause Zika and dengue. There is a rush to do so, as many frog populations have plummeted in recent years due to habitat loss, pollution, climate change, infectious diseases like chytridiomycosis that are spread by human activity, and other human-associated threats.

“Frogs have been around for a long time and can usually fight what life brings them, but not what man brings them,” Jacob said. He explained that human-caused changes can happen too quickly for frogs to evolve appropriate survival responses, such as new defense peptides.

“We don’t want frogs and other amphibians to become extinct,” he added. “They are a huge resource for potential cures for human illnesses.”

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