Neutralizing deadly snake toxins

The blog post originally published on Baker’s Lab details an innovative breakthrough in addressing one of the world’s most neglected tropical health crises: snakebite envenomation. According to data cited in the post, the World Health Organization estimates that venomous snakes kill over 100,000 people annually and leave approximately 300,000 others with permanent disabilities including amputated limbs. This public health burden disproportionately affects regions with limited healthcare infrastructure.

The research team, led by Susana Vázquez Torres in collaboration with the Digital Biotechnology Lab at the Technical University of Denmark, has developed a novel approach using artificial intelligence to design specialized proteins that can neutralize deadly snake toxins. This represents a significant departure from traditional antivenom production methods, which rely on animal immunization processes that are costly, resource-intensive, and often result in products with considerable side effects.

The scientists focused specifically on elapid snakes—a family that includes highly venomous species like cobras and mambas. These snakes produce particularly dangerous three-finger toxins that cause paralysis and cellular death by interfering with nerve-muscle communication. Current antivenoms frequently struggle to effectively neutralize these specific toxin types, making this research particularly valuable.

By leveraging advanced protein design methods and AI-powered software, the team created small, stable proteins capable of binding to critical regions of these toxins. Laboratory testing confirmed that these designed proteins could neutralize multiple subtypes of three-finger toxins. The effectiveness of these artificial proteins was further validated through mouse studies, where they demonstrated remarkable protection rates of 80-100% against lethal neurotoxin exposure, depending on the specific toxin-antitoxin combination.

Tim Jenkins, an associate professor at DTU Bioengineering and co-senior author of the study, emphasized the efficiency of their computational approach: “By designing binding proteins entirely on the computer using AI-powered software, we dramatically cut the time spent in the discovery phase. We didn’t need to perform several rounds of laboratory experiments to find proteins that performed well—the design software is so good now that we only needed to test a few molecules.”

The blog post outlines several advantages of these “miniproteins” over traditional antivenoms. First, they can be manufactured through recombinant production methods, eliminating dependence on animal immunization and ensuring consistent quality. Second, their compact structure potentially allows for deeper tissue penetration, which could accelerate toxin neutralization. Third, like most computationally designed proteins, these miniproteins demonstrate excellent thermal stability, remaining folded and active even at high temperatures—a characteristic that would simplify transportation and extend storage life in tropical regions where snakebites are most common.

Importantly, the researchers report that these new proteins showed no adverse effects in animal studies, a crucial milestone toward developing safe human therapies. While traditional antivenoms will continue to be the primary treatment for snakebite victims in the immediate future, these AI-designed antitoxins could complement existing treatments or enhance their effectiveness.

The post concludes by highlighting the broader implications of this technology beyond snakebite treatment. David Baker notes that “Beyond treating snakebites, protein design will help simplify and democratize drug discovery, particularly in resource-limited settings. By lowering costs and resource requirements for protein-based medicines, we’re taking considerable steps toward a future where everyone can get the treatments they deserve.”

This collaborative project involved researchers from multiple prestigious institutions including the University of Washington Institute for Protein Design, University of Northern Colorado, Liverpool School of Tropical Medicine, Lancaster University, Sophion Bioscience, University of Liverpool, and Massachusetts Institute of Technology. The research received support from numerous funding organizations, including the Open Philanthropy Project, Audacious Project, Howard Hughes Medical Institute, Novo Nordisk Foundation, and the Wellcome Trust, reflecting the significant interest in and potential impact of this innovative approach to treating snakebite envenomation.