Rattlesnake Blood Proteins Point to More Powerful Antivenom

Researchers at the University of Maryland (UMD) have identified toxin-blocking proteins in the blood of western diamondback rattlesnakes that could help scientists develop a more powerful antivenom, a treatment used to counter snakebite poisoning. The proteins are natural defenses snakes evolved against their own venom. The study, led by Sean B. Carroll, Distinguished University Professor of Biology at UMD, was published in the Proceedings of the National Academy of Sciences (PNAS).

Snakebite is considered one of the world's most neglected tropical diseases. The World Health Organization estimates venomous snakes kill 80,000 to 140,000 people annually, while hundreds of thousands of survivors are left permanently disabled, often in rural areas with limited access to antivenom. Existing antivenoms are typically made by exposing horses or sheep to snake venom and collecting the antibodies they produce, which can be costly, vary in quality, and cause serious immune reactions.

In 2022, Carroll's laboratory identified one such protein, called FETUA-3, which blocks metalloproteinases, venom enzymes that damage tissue and blood vessels, in western diamondback rattlesnake venom and also inhibits toxins from several other rattlesnake species. Working with co-authors including Elda Sánchez of Texas A&M University-Kingsville, the team found that each individual FETUA protein could counter only certain venom effects, one reduced bleeding and another blocked enzyme activity, but none alone fully prevented death from a venomous bite.

When the researchers combined several FETUA proteins, the mixtures blocked venom far more effectively than any single protein. In laboratory experiments, optimized combinations were about ten times more potent than current sheep-based rattlesnake antivenom, completely neutralizing rattlesnake venom's lethal effects and providing broad protection against venom from multiple viper species, including species separated by millions of years of evolution.

The study focused on metalloproteinases, one of three major toxin families in viper venom; the researchers are now targeting the other two. The work was funded by the Howard Hughes Medical Institute and the Viper Resource Center.