Mucus secreted from the skin of the Hydrophylax bahuvistara frog may kill certain strains of the flu virus.
The discovery was published in Immunity and was led by senior author Joshy Jacob, Ph.D., associate professor of microbiology and immunology at the Emory Vaccine Center and Emory University School of Medicine.
Prof. Jacob and graduate student David Holthausen collaborated on the research project with M.R. Pillai, Ph.D., and Sanil George, Ph.D., from the Rajiv Gandhi Center for Biotechnology.
Previous research has shown that frogs' skins secrete mucus that contains "host defense peptides," known to protect them from harmful bacteria. The new study reveals that the skin secretions from South Indian frogs act as "anti-flu peptides" and could prove useful in the antiviral drug arena.
For example, anti-flu peptides could be an invaluable resource if there were a new influenza pandemic. Influenza pandemics occur when there is an outbreak of a novel influenza strain that emerges, infects, and spreads quickly and easily. In the absence of a vaccine for the new strain, or if strains that are already circulating become resistant to current drugs, anti-flu peptides could be utilized.
A peptide is a tiny compound made from a small chain of amino acids, commonly referred to as the "building blocks of proteins." Prof. Jacob and team called one of the antiviral peptides they discovered "urumin," after a whip-like sword used many years ago in the south of India called the "urumi."
The team used mild electrical stimulation to collect urumin from the skin secretions of the Indian frog Hydrophylax bahuvistara. Some antibacterial peptides are poisonous to mammalian cells and work by punching holes in the cell membranes. However, when viewing urumin through electron microscopy, the researchers uncovered that the peptide only disrupted the flu virus' integrity.
Jacob notes that urumin attaches to the stem region of the viral hemagglutinin protein - a part of the virus responsible for binding the virus to the infected cell. "This specificity could be valuable because current anti-influenza drugs target other parts of the virus," says Prof. Jacob.
This region of the flu virus is also the target of the proposed universal flu vaccine, a new generation of vaccines that protect against multiple strains of flu.
Urumin effective against H1 influenza virus strains
According to the World Health Organization (WHO), annual influenza epidemics affect around 5 to 15 percent of the population of the northern hemisphere. Currently, the most efficient way to prevent flu for people who are most at risk of serious complications is to have an annual vaccination.
The Centers for Disease Control and Prevention (CDC) recommend that all individuals 6 months of age and older should be vaccinated against the flu every season.
In an experiment, the researchers identified that administering urumin to unvaccinated mice through the nose protected them against a lethal dose of flu. However, the protection was only specific to some strains of flu. Urumin worked against the H1 strains of flu - the 2009 pandemic strain - but were not effective against other current flu strains, such as H3N2. The infectious agent from which urumin protects frogs is currently unknown.
"Because flu viruses from humans cannot infect frogs, producing urumin probably confers on frogs an advantage in fighting some other pathogen."
Joshy Jacob, Ph.D.
Developing antimicrobial peptides from frogs' skins into active drugs is challenging since the body's enzymes can break them down. Future work by Jacob and colleagues will center on exploring ways to stabilize urumin and other antiviral peptides. The team also aims to search for other frog-derived peptides that might tackle viruses including dengue and Zika.