Nobel Laureate David Baker’s team has designed new proteins that effectively neutralize dangerous snake toxins, showing promise for transforming snakebite treatments worldwide with safer, cheaper, and more effective solutions.
A groundbreaking study led by Nobel Laureate David Baker and Timothy Patrick Jenkins introduces innovative, computationally designed proteins that can neutralize lethal snake venom toxins, offering potential for safer, more effective, and cost-efficient treatments.
This new approach promises to significantly improve outcomes for the millions affected by venomous snakebites globally, particularly in under-resourced regions.
Breakthrough in Snakebite Treatment
A groundbreaking study published today (January 15) in Nature by this year’s Nobel Laureate in Chemistry introduces a potential game-changer in snakebite treatment. Scientists have developed innovative proteins capable of neutralizing lethal snake venom toxins, offering a promising, safer, and more effective alternative to traditional antivenoms.
The World Health Organization (WHO) reports that venomous snakebites affect 1.8 to 2.7 million people annually, resulting in approximately 100,000 deaths each year and leaving three times as many individuals with permanent disabilities, such as amputations. The majority of these cases occur in Africa, Asia, and Latin America, where limited healthcare infrastructure worsens the problem.
Currently, the only antivenoms used to treat snakebite victims are derived from animal plasma and often come with high costs, limited efficacy, and adverse side effects. Venoms also differ widely across snake species, necessitating custom treatments in different parts of the world. In recent years, however, scientists have gained a deeper understanding of snake toxins and developed new ways to combat their effects. One such development is published today in Nature.
The new study reveals potential for safer, more efficient snakebite treatments through proteins designed via computational methods, aiming to drastically reduce the global snakebite burden. Credit: University of Washington
Revolutionary Antivenoms Developed
A team led by 2024 Nobel Laureate in Chemistry David Baker from the University of Washington School of Medicine and Timothy Patrick Jenkins from DTU (the Technical University of Denmark) used deep learning tools to design new proteins that bind to and neutralize toxins from deadly cobras.
The study focuses on an important class of snake proteins called three-finger toxins, which are often the reason antivenoms based on immunized animals fail.
While not yet protecting against full snake venom — which is a complex mixture of different toxins unique to each snake species—the AI-generated molecules provide full protection from lethal doses of three-finger toxins in mice: 80-100% survival rate, depending on the exact dose, toxin, and designed protein.
These toxins tend to evade the immune system, rendering plasma-derived treatments ineffective. This research thus demonstrates that AI-accelerated protein design can be used to neutralize harmful proteins that have otherwise proven difficult to combat.
“I believe protein design will help make snake bite treatments more accessible for people in developing countries,” said Susana Vazquez Torres, lead author of the study and a researcher in Baker’s lab at the Institute for Protein Design at UW Medicine.
“The antitoxins we’ve created are easy to discover using only computational methods. They’re also cheap to produce and robust in laboratory tests,” said Baker.
The scientists reasoned that creating proteins that stick to and disable snake toxins could create several advantages over traditional treatments. The new antitoxins can be manufactured using microbes, circumventing traditional animal immunization and potentially slashing production costs.
But there are more advantages, explains Timothy Patrick Jenkins, an Associate Professor at DTU Bioengineering:
“The most remarkable result is the impressive neurotoxin protection they afforded to mice. However, one added benefit of these designed proteins is that they are small—so small, in fact, that we expect them to penetrate tissue better and potentially neutralize the toxins faster than current antibodies. And because the proteins were created entirely on the computer using AI-powered software, we dramatically cut the time spent in the discovery phase. ”
Future Prospects and Wider Applications
Although these results are encouraging, the team stresses that traditional antivenoms will remain the cornerstone in treating snakebites for the foreseeable future. The new computer-designed antitoxins could initially become supplements or fortifying agents that improve the effectiveness of existing treatments until standalone next-generation therapies are approved.
According to the scientists, the drug development approach described in this study could also be useful for many other diseases that lack treatments today, including certain viral infections. Because protein design generally requires fewer resources than traditional lab-based drug discovery methods, there is also the potential to generate new but less costly medicines for more common diseases using a similar approach.
“We didn’t need to perform several rounds of laboratory experiments to find antitoxins that performed well — the design software is so good now that we only needed to test a few molecules,” said Baker. “Beyond treating snake bites, protein design will help simplify drug discovery, particularly in resource-limited settings. By lowering costs and resource requirements for potent new medicines, we’re taking considerable steps toward a future where everyone can get the treatments they deserve.”
Reference: “De novo designed proteins neutralize lethal snake venom toxins” by Susana Vázquez Torres, Melisa Benard Valle, Stephen P. Mackessy, Stefanie K. Menzies, Nicholas R. Casewell, Shirin Ahmadi, Nick J. Burlet, Edin Muratspahić, Isaac Sappington, Max D. Overath, Esperanza Rivera-de-Torre, Jann Ledergerber, Andreas H. Laustsen, Kim Boddum, Asim K. Bera, Alex Kang, Evans Brackenbrough, Iara A. Cardoso, Edouard P. Crittenden, Rebecca J. Edge, Justin Decarreau, Robert J. Ragotte, Arvind S. Pillai, Mohamad Abedi, Hannah L. Han, Stacey R. Gerben, Analisa Murray, Rebecca Skotheim, Lynda Stuart, Lance Stewart, Thomas J. A. Fryer, Timothy P. Jenkins and David Baker, 15 January 2025, Nature.
DOI: 10.1038/s41586-024-08393-x
