Proteins from rattlesnake blood beat the antivenom in use by a factor of ten

Snakebite kills as many as 140,000 people a year worldwide, and the antivenom used to treat it has barely changed in a century. A team at the University of Maryland says it has found a strikingly effective alternative hiding in the blood of the very snake most antivenom is designed to counter: the western diamondback rattlesnake. In laboratory tests, combinations of the rattlesnake’s own toxin-blocking proteins neutralized venom about ten times more effectively than a current commercial antivenom, and did so against several viper species at once.

The Global Toll of a Neglected Disease

Snakebite is classified by the World Health Organization as one of the world’s most neglected tropical diseases, with venomous snakes killing an estimated 80,000 to 140,000 people annually and leaving hundreds of thousands more with permanent injuries. Most of that burden falls on rural communities in parts of Africa, Asia and Latin America where effective antivenom is hard to reach. Existing antivenoms are produced by injecting venom into large animals, usually horses or sheep, and then harvesting the antibodies those animals generate, a process that is expensive, inconsistent in potency, and prone to triggering serious immune reactions in patients.

A Century-Old Clue in the Snake’s Own Blood

Sean B. Carroll, a distinguished professor of biology at the University of Maryland who led the study, said scientists have known anecdotally for a hundred years that vipers are largely resistant to their own venom, but nobody had identified the specific proteins responsible, according to the University of Maryland’s summary of the research. His lab found part of the answer in 2022: a protein called FETUA-3 that blocks many of the metalloproteinase toxins found in diamondback venom and also neutralizes related toxins from several other rattlesnake species. The new study, published in the Proceedings of the National Academy of Sciences, examined what each individual FETUA protein contributes to that resistance, working with co-author Elda Sánchez of the National Natural Toxins Research Center at Texas A&M University-Kingsville.

Carroll described the project as one of those rare moments when a problem researchers had chased for decades turns out to already have a solution built into the natural world. That reframing changed the guiding question for his lab: rather than continuing to refine antibody production in horses, the team asked why an effective antidote already circulating in rattlesnake blood was not simply being isolated and copied directly.

Combinations Succeed Where Single Proteins Fall Short

On their own, individual FETUA proteins could blunt specific effects of venom, one reducing bleeding, another interfering with enzyme activity, but none could fully prevent a lethal outcome by itself. That changed when researchers combined several proteins together. Because a single snake venom can contain around 100 different toxin proteins spanning multiple families, and venom composition varies from species to species, finding the right combination required extensive trial and error. The optimized mixtures the team eventually landed on fully neutralized the lethal effects of rattlesnake venom in lab tests and extended broad protection to venom from other viper species, including some separated from the diamondback by tens of millions of years of evolution.

Conserved Proteins Reveal a Real Evolutionary Risk

Carroll noted that parts of these venom-blocking proteins have remained essentially unchanged across roughly 50 million years of snake evolution, a level of conservation that signals how real the threat of self-envenomation has been for vipers throughout their history. Scientists still are not certain exactly how snakes are exposed to their own venom, whether through minor mouth injuries during a bite, by consuming already-envenomated prey, through cannibalism, or some combination of all three, but the persistence of these protective proteins suggests the risk has shaped viper biology for a very long time.

Toward a Nature-Based Antivenom

The Maryland team is now applying the same strategy to other major toxin families found in viper venom beyond metalloproteinases, with Carroll saying the lab is “getting remarkably close” to solutions for the three main toxin classes vipers produce. He expects the first practical use of the approach to arrive in veterinary medicine, where treatments for snakebitten livestock and pets could reach the market before a human version clears the additional regulatory hurdles required for clinical use. The research was funded by the Howard Hughes Medical Institute and the Viper Resource Center, and the authors say a lab-produced, recombinant version of the protein combinations could eventually be manufactured at large scale, offering a more consistent and less allergenic alternative to antivenom derived from horse or sheep blood.

Scaling a Solution That Nature Already Built

Carroll has described the long-term ambition in blunt terms, saying the approach could eventually produce enough recombinant antivenom to fill “train cars-worth” of the material and help address a global health problem that has gone underfunded relative to its death toll. Because the proteins can be manufactured through recombinant methods rather than harvested from immunized livestock, the team argues that supply would no longer hinge on maintaining herds of venom-producing horses or sheep, a bottleneck that has long limited antivenom availability in the low-income regions where snakebite deaths are most concentrated. Carroll has also pointed to the irony that one of medicine’s most promising new antivenom candidates was never hidden in a remote rainforest or deep-sea vent, but circulating all along in a snake most people in the American Southwest already know to avoid.

This article was created with the assistance of AI and reviewed by an editor.

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