Combinations of rattlesnake blood antivenom proteins can neutralise venom from several dangerous snake species at roughly ten times the potency of a current commercial antivenom, according to a study published on 29 July 2026 in the Proceedings of the National Academy of Sciences. The research, led by Sean B. Carroll at the University of Maryland, draws on a defence mechanism the snakes evolved for themselves, and raises the prospect of a new class of nature-derived snakebite treatments.
The findings are not a finished antivenom. They are a laboratory result, and Carroll is careful to say so. But the scale of the problem they are aimed at gives the work its weight.
A neglected disease with a staggering toll
Snakebite is classed as one of the world’s most neglected tropical diseases. According to the World Health Organization, venomous snakes kill an estimated 80,000 to 140,000 people annually, while hundreds of thousands of survivors are left with permanent disabilities. Many of those affected live in rural areas where effective antivenom is difficult to obtain.
Existing antivenoms do save lives, but they carry well-documented drawbacks. They are typically produced by exposing large animals to snake venom and collecting the antibodies those animals generate. Manufacturing costs are high, quality and effectiveness can vary, and they may not work equally well against the many different toxins found across snake species. They can also trigger serious immune reactions.
What the rattlesnake blood antivenom proteins actually are
The starting point for the new work was a protein called FETUA-3, which Carroll’s laboratory identified in 2022. The team found it could block the activity of many metalloproteinase toxins found in western diamondback rattlesnake venom, and could also bind to and inhibit toxins from the venoms of several other rattlesnake species. ‘Here was evolution’s way for snakes to protect themselves from accidental self-envenomation,’ Carroll said.
For the current study, co-authors including Elda Sánchez, director of the National Natural Toxins Research Center at Texas A&M University-Kingsville, examined what each FETUA protein contributes to venom resistance in isolation. The picture was mixed. Individual proteins could counter certain effects: one might reduce bleeding, another could interfere with enzyme activity. But none of the FETUA proteins on its own was able to completely prevent death from a venomous bite.
The results changed when the team began combining them. Mixtures of FETUA proteins proved far more effective at blocking the harmful effects of venom than any single protein alone. In laboratory experiments, optimised combinations were about ten times more potent than the current sheep-derived rattlesnake antivenom, and completely neutralised the lethal effects of rattlesnake venom. The mixtures also provided broad protection against venom from multiple viper species, including species separated by millions of years of evolution.
Snake venom is extraordinarily complex: a single venom can contain around 100 toxin proteins belonging to multiple protein families, and composition differs from one species to another. Finding the best combinations is therefore not straightforward. ‘The ingredients are there,’ Carroll said. ‘We just have to keep testing various mixtures.’
‘The fact that parts of these inhibitors have been perfectly conserved over 50 million years of snake evolution tells you just how real a risk this is for these animals,’ Carroll added. How snakes actually envenomate themselves, whether through mouth tissue during a bite, by eating envenomated prey, through cannibalism, or all of the above, remains poorly understood.
From lab result to possible clinical application
The present study concentrated on metalloproteinases, one important toxin family. The researchers are now applying the same strategy to other toxin families found in viper venom. ‘We’re getting remarkably close to having effective solutions for the three major toxin families in vipers,’ Carroll said. ‘What we’ve learned here, together with research we’re doing now, gives us real confidence that nature-based recombinant antivenoms are within reach.’
Carroll expects that the first commercial applications could be in veterinary medicine, with treatments for human snakebites potentially following later. He envisions future antivenoms that protect against a wider range of venoms while being safer, less expensive, and easier to manufacture at scale than many current treatments. ‘Why rely on horse antibodies when nature has packaged an effective antidote right there in the snake?’ he said.
The paper, whose full details are reported by the University of Maryland College of Computer, Mathematical, and Natural Sciences, also lists UMD co-authors Fiona Ukken and Yetunde Ayinuola. The research was funded by the Howard Hughes Medical Institute and the Viper Resource Center. The next test is whether the protein combinations hold up beyond the lab, but Carroll’s stated ambition is clear enough: ‘We could make train cars-worth of this stuff and help solve a massive global health problem.’
