University of Maryland researchers discovered a new approach to treating venomous snake bites—using the same toxin-blocking proteins that snakes evolved to protect themselves. The team found that specific combinations of blood proteins from western diamondback rattlesnakes provided unprecedented neutralizing power against the venom of multiple dangerous snake species.

The research, led by Distinguished University Professor of Biology Sean B. Carroll and published July 29, 2026 in the Proceedings of the National Academy of Sciences, offers a promising way to formulate more potent antivenoms against deadly snakebites—a significant problem in some parts of the world.

“This is one of those great stories when nature has already solved a problem we’ve been grappling with for decades,” said Carroll, who also holds the Andrew and Mary Balo and Nicholas and Susan Simon Endowed Chair at UMD.

Snakebites remain one of the world’s most neglected tropical diseases. The World Health Organization estimates that venomous snakebites kill 80,000 to 140,000 people each year and leave hundreds of thousands more with permanent disabilities. Many victims live in rural regions where access to effective antivenoms is limited.

And while they do save lives, today’s antivenoms—made by immunizing large animals with snake venom and harvesting the resulting antibodies—are expensive to manufacture, vary in quality and effectiveness against the wide array of venom toxins from different snake species, and can trigger severe immune reactions. These limitations drive researchers to identify a better way of treating snakebites—in this case, by going back to the source.

“We’ve known from anecdotes for 100 years that vipers tend to be resistant to their own venom,” Carroll said. “But for a long time, nobody knew what exactly was circulating in their blood that protected them.”

In 2022, Carroll’s lab found part of the answer: a single protein called FETUA-3 that blocked the activity of many metalloproteinase toxins in the western diamondback’s venom. FETUA-3 also bound to and inhibited the toxins of venoms from several other rattlesnakes.

“Here was evolution’s way for snakes to protect themselves from accidental self-envenomation,” he said, which prompted a follow-up question. “Why rely on horse antibodies when nature has packaged an effective antidote right there in the snake?”

For the new study, co-authors including Elda Sánchez, who directs the National Natural Toxins Research Center at Texas A&M University-Kingsville, investigated the individual roles of all FETUA proteins. They found that while one FETUA protein might reduce bleeding and another might affect enzyme activity, no one FETUA protein completely prevented death from a bite.

However, combining several of these proteins dramatically increased their ability to neutralize venom’s damaging effects. Because a single venom might contain 100 toxin proteins from multiple protein families and no two species’ venoms are the same, the scientists have their work cut out for them finding the most effective combinations of toxin inhibitors.

“The ingredients are there,” Carroll said. “We just have to keep testing various mixtures.”

In laboratory tests, optimized protein combinations proved about 10 times more potent than the current sheep-derived rattlesnake antivenom; they completely neutralized rattlesnake venom lethality and provided broad protection against venoms from multiple viper species—even some separated by millions of years of evolution.

“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 said, noting that how snakes envenomate themselves—whether through mouth tissue during a bite, by eating envenomated prey, through cannibalism or all of the above—isn’t well understood.

While the current study focused on metalloproteinases, the researchers are now applying the same strategy to additional venom toxin families.

“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 [lab-produced] antivenoms are within reach.”

Carroll believes the first commercial uses of “nature’s antivenom” may be veterinary, followed by treatments for snakebites in humans, and that the next generation of antivenoms will provide broader protection than today’s versions while being safer, more affordable and easier to manufacture at large scale.

“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.”

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In addition to Carroll, study co-authors from UMD included Department of Biology visiting faculty specialists Fiona Ukken and Yetunde Ayinuola.

The paper, “Nature’s antivenom: Combinations of conserved rattlesnake serum metalloproteinase inhibitors block the lethal action of viper venoms,” was published in Proceedings of the National Academy of Sciences on July X, 2026.

This work was funded by the Howard Hughes Medical Institute and the Viper Resource Center (Grant #P40OD01960-22). This article does not necessarily reflect the views of these organizations.

Journal

Proceedings of the National Academy of Sciences

Funder

Howard Hughes Medical Institute,
Viper Resource Center

DOI

10.1073/pnas.2612168123

Snakebite envenoming is a neglected tropical disease that causes upwards of 100,000 to 150,000 fatalities annually worldwide, particularly afflicting rural populations in sub-Saharan Africa. Survivors often endure severe disabilities such as tissue necrosis and amputations, consequences of venom-induced cytotoxicity and insufficient access to effective treatment. Traditional antivenoms, derived from the plasma of horses immunized with snake venom, suffer from multiple inherent limitations. They offer narrow specificity, often targeting only a subset of toxins, and come with the risk of adverse immune reactions due to the introduction of large, heterogeneous antibody mixtures.

The DTU-led team, under the guidance of Professor Andreas Hougaard Laustsen-Kiel, has addressed these issues by developing a novel recombinant antivenom utilizing nanobodies—single-domain antibody fragments naturally found in camelid species. These nanobodies, distinctively small and structurally robust, demonstrate superior tissue penetration and can be engineered to bind with high affinity and specificity to a wide array of venom toxins. Unlike conventional polyclonal antivenoms, this approach offers reproducibility, scalability, and potentially reduced immunogenicity.

In laboratory settings, the antivenom cocktail, composed of eight meticulously selected nanobody clones, has demonstrated remarkable neutralization capacity against venoms from 17 medically significant African snake species belonging to genera such as Naja (cobras), Dendroaspis (mambas), and Hemachatus (rinkhals). This broad coverage is unprecedented, given the vast interspecies variation in venom profiles—ranging from neurotoxic components that impair neurotransmission in cape cobras to potent cytotoxins in spitting cobras that devastate local tissues.

Current standard-of-care antivenoms are produced via immunization protocols involving multiple horses, resulting in batch-to-batch variability and large immunogenic protein loads. These factors complicate treatment and occasionally provoke serum sickness or anaphylaxis, particularly when administered repeatedly or in delayed fashion. On the contrary, nanobody-driven antivenoms benefit from recombinant production systems, thus reducing variability and side effect prevalence. Moreover, nanobodies’ smaller size and enhanced stability facilitate more effective neutralization of both systemic neurotoxins and localized cytotoxins.

Another critical advantage emerges from the recombinant platform’s manufacturing potential. Nanobody therapies can be produced with high precision at scale using microbial fermentation, circumventing the ethical and logistical concerns associated with the maintenance of large equine herds. Economic modeling by the researchers suggests that production costs could fall to less than half of that of existing antivenoms. Cost savings coupled with greater physico-chemical stability imply more reliable storage and distribution, essential factors for resource-limited settings where cold-chain infrastructure is scarce.

Despite the promising preclinical findings, the research acknowledges current limitations concerning post-envenomation treatment timing and efficacy against some highly lethal species like the black mamba and forest cobra. The venom composition in these snakes remains exceptionally complex, involving multivalent toxins that require further optimization of the nanobody cocktail. The team remains actively engaged in iterative nanobody engineering and selection to enhance breadth, potency, and pharmacokinetics.

The translational pathway to clinical deployment involves critical steps, including human safety and efficacy trials, regulatory approval, and manufacturing scale-up. The researchers project that, contingent on securing necessary funding and partnerships, first-in-human trials could commence within one to two years. A fully developed product might be market-ready within three to four years, potentially revolutionizing snakebite treatment paradigms and saving tens of thousands of lives annually.

Addressing the socio-economic barriers that hinder antivenom availability in high-burden regions remains a focal concern. Historically, poor purchasing capacity in many African countries has deterred investment in antivenom innovation and production. Nonetheless, by reducing reliance on animal-derived materials and lowering costs significantly, this recombinant antivenom model may attract broader stakeholder interest and facilitate integration into public health programs.

The innovative use of phage display technology to design recombinant nanobodies tailored for venom neutralization exemplifies a new frontier in biotherapeutics. This approach offers a template for tackling other toxin-mediated diseases where current antibody therapies are inadequate. Moreover, through the detailed characterization of venom epitopes and antibody binding dynamics, the work contributes valuable insights into venom biochemistry and immunology that extend beyond antivenom development.

Ultimately, Professor Laustsen-Kiel and his colleagues envision this recombinant antivenom as a transformative solution to a global health challenge that has long resisted effective pharmacological intervention. Their work underscores the intersection of molecular engineering, synthetic biology, and tropical medicine, heralding an era in which snakebite envenoming may finally be met with precise, safe, and broadly accessible treatments. The promising results published in the journal Nature mark a pivotal milestone, opening pathways to a future where snakebite mortality and morbidity can be dramatically reduced through innovative science.

Subject of Research: Development of a broad-spectrum recombinant nanobody-based antivenom targeting venomous African snakes including cobras, mambas, and rinkhals.

Article Title: Nanobody-based recombinant antivenom for cobra, mamba and rinkhals bites

News Publication Date: 29-Oct-2025

Web References:

• Nature Article DOI: 10.1038/s41586-025-09661-0
• World Health Organization Snakebite Envenoming Fact Sheet

Image Credits: Photo of Yellow Cape cobra (Naja nivea) by Wolfgang Wüster

Keywords: Snakebite envenoming, nanobodies, recombinant antivenom, phage display technology, Africa, venom neutralization, tropical disease, biotechnology, antibody engineering, toxin biochemistry