After success finding flu virus-killing peptides in frog slime, immunologist Joshy Jacob and his colleagues at Emory Vaccine Center turned their attention from influenza to Zika. Their follow-up paper on an antiviral peptide that destroys Zika virus was published earlier this year in Scientific Reports.
The findings illustrate how frogs’ skin secretions are a rich source of potential antiviral weapons, even though Zika itself is not thought to infect frogs. Jacob reports his team is currently investigating peptides with activity against SARS-CoV-2. Lab Land is expecting to hear more about that soon.
But before SARS-CoV-2, you may recall Zika as a virus of public health concern. Carried by mosquitoes, its insidious infection can lead to neurological birth defects and disabilities in infants and Guillain-Barre syndrome in adults. Neither antiviral drugs or vaccines are available against Zika, leaving the field wide open for Jacob’s amphibian approach.
Jacob and his crew decided to call their antiviral Zika-destroying peptide Yodha, which means “warrior” in Sanskrit. Just in case you might have some other associations for that word, which sounds like the name of a few recent Bollywood movies, as well as a diminutive Jedi trainer from the Star Wars universe.
The Yodha peptide emerged from a screen of many frog peptides, and it was the only one of several Zika-killing peptides that was not toxic to human red blood cells. The peptide comes from the skin of Indosylvirana aurantiaca which lives in the western Ghats of India and is commonly known as the “golden frog.” (The website India Biodiversity, linked above, has photos of the frogs.)
Using electron microscopy, Jacob’s lab could show that the Yodha peptide blasts Zika virus particles apart with a few minutes of exposure. It was active against Zika and all four varieties of the related dengue virus.
With Jacob’s previous work on anti-flu peptides, showing in vivo activity was the challenging part. Pharmacologists would be concerned about how long the peptides would last in the body, because enzymes would break them down quickly. Here, both the naturally occurring L-form and the mirror image D-form were active against Zika virus, so using D-peptides may slow their degradation and aid in pharmaceutical delivery. The researchers could show that subcutaneous injection of Yodha peptide could reduce viral loads in a mouse model of Zika infection.
The first author of the Yodha paper, former Emory postdoc Song Hee Lee, is now a research director at Ubix Therapeutics in South Korea.