Scientists Uncover Potent Rattlesnake-Derived Antivenom in Lab Tests

Researchers at the University of Maryland have identified a novel therapeutic approach for treating venomous snakebites by harnessing the natural immune defenses of the snakes themselves. The study, led by Distinguished University Professor of Biology Sean B. Carroll and published in the Proceedings of the National Academy of Sciences, demonstrates that specific proteins found in western diamondback rattlesnake blood can effectively neutralize venom.

By blending these toxin-blocking proteins, the research team achieved remarkably strong protection against venom from multiple dangerous snake species. Carroll, who also holds the Andrew and Mary Balo and Nicholas and Susan Simon Endowed Chair at UMD, described the findings as a significant breakthrough.

“This is one of those great stories when nature has already solved a problem we’ve been grappling with for decades,” Carroll said. “We’ve known from anecdotes for 100 years that vipers tend to be resistant to their own venom, but for a long time, nobody knew what exactly was circulating in their blood that protected them.”

The development addresses a critical global health issue. The World Health Organization identifies snakebite as one of the world’s most neglected tropical diseases, estimating that venomous snakes kill between 80,000 and 140,000 people annually. Hundreds of thousands more survivors endure permanent disabilities, often in rural areas where access to effective treatment is limited.

Current antivenoms, typically produced by extracting antibodies from large animals exposed to venom, present several challenges. Manufacturing is costly, efficacy can vary, and the treatments may not counteract all toxins across different snake species. Additionally, they can trigger severe immune reactions in patients.

The journey to this discovery began in 2022 when Carroll’s lab identified a protein named FETUA-3. They found it could block metalloproteinase toxins in western diamondback rattlesnake venom and inhibit toxins from other rattlesnake species. This prompted the question of whether nature already contained the antidote within the snake.

For the latest research, the team, including co-author Elda Sánchez from Texas A&M University-Kingsville, analyzed the contributions of various FETUA proteins. While individual proteins could mitigate specific venom effects, such as reducing bleeding or interfering with enzymes, none could alone prevent death from a bite.

However, combining multiple FETUA proteins resulted in a dramatic increase in protective power. Because snake venom is complex—containing roughly 100 different toxin proteins—the researchers had to test numerous combinations. The optimized mixtures proved approximately 10 times more potent than existing sheep-derived rattlesnake antivenom.

In laboratory settings, these protein combinations completely neutralized lethal rattlesnake venom and offered broad protection against venoms from various viper species. Carroll noted that the conservation of these inhibitors over 50 million years of evolution highlights the persistent risk snakes face from accidental self-envenomation.

Although the current study focused on metalloproteinases, the team is applying the same strategy to other toxin families. Carroll expressed confidence that effective, nature-based recombinant antivenoms are approaching reality.

He anticipates that veterinary medicine will likely see the first commercial applications of these “nature’s antivenom” treatments, with human therapies potentially following. The goal is to produce safer, less expensive, and more scalable antivenoms that can address a wider range of snakebites.

“We could make train cars-worth of this stuff and help solve a massive global health problem,” Carroll said. “Many of our most important medicines have come from nature. I’m delighted that the components for a better-than-commercial antivenom were in these snakes all along.”

Along with Carroll, UMD co-authors included Fiona Ukken and Yetunde Ayinuola. The research received funding from the Howard Hughes Medical Institute and the Viper Resource Center.