Engineered Proteins Revolutionize Snakebite Antivenom

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Researchers have developed novel proteins using computational design to neutralize specific toxins found in the venom of certain poisonous snakes. This approach may lead to more efficient, safer and less expensive alternatives to current antivenom therapies.

Snakebites as a global health concern

Snakebites affect over 2 million people annually, causing more than 100,000 deaths and 300,000 cases of severe complications like paralysis or amputation. Regions such as Sub-Saharan Africa, South Asia, Papua New Guinea and Latin America bear the brunt of these public health challenges.

Antivenom production typically involves using antibodies derived from immunized animals, which can be costly and have limited efficacy against specific venom components. These treatments also pose risks such as allergic reactions or respiratory distress. Researchers have aimed to improve these methods by employing cutting-edge protein design.

“Efforts to try to develop new drugs have been slow and laborious,”

Susana Vazquez Torres.

Computationally designed proteins target toxins

The study, conducted by the UW Medicine Institute for Protein Design and the Technical University of Denmark, focused on neutralizing three-finger toxins – potent components of elapid snake venom. Elapids, a family of snakes that includes cobras and mambas, use their venom to disrupt nerve and muscle communication, leading to tissue damage, paralysis and potential death.

Three-finger toxins

A class of toxic proteins found in snake venom that disrupt cellular signaling and cause neurotoxic effects, including paralysis and death. Named for their structural resemblance to a three-fingered hand.

Using deep learning algorithms, researchers designed proteins to bind with and neutralize these toxins. The designs were tested for thermal stability and binding affinity, resulting in proteins that closely matched their computational blueprints. Lab experiments confirmed their effectiveness against three distinct subfamilies of three-finger toxins.

Benefits of protein-based antivenoms

In mice, the designed proteins protected against lethal doses of neurotoxin, demonstrating their potential as effective antivenoms. Unlike traditional treatments, these proteins can be synthesized through recombinant DNA technology, which allows for consistent manufacturing quality without the need for animal immunization.

Recombinant DNA technology

A method that uses genetic engineering to create DNA molecules by combining genetic material from different sources. This process enables the production of proteins in laboratory settings, bypassing the need for natural sources such as animal plasma.

The smaller size of these proteins compared to antibodies may improve their ability to penetrate tissues and act more rapidly against toxins. The researchers noted that similar computational methods could be applied to other neglected diseases, offering a cost-efficient route to develop new therapies for resource-limited settings.

Reference: Vázquez Torres S, Benard Valle M, Mackessy SP, et al. De novo designed proteins neutralize lethal snake venom toxins. Nature. 2025. doi: 10.1038/s41586-024-08393-x

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