Scientists have successfully engineered new proteins that do not exist in nature to combat certain highly toxic elements found in snake venom. Utilizing advanced deep learning and computational techniques, they aim to develop safer, more affordable, and more accessible treatments compared to current options.
Annually, over 2 million individuals experience snakebites, with the World Health Organization estimating that more than 100,000 die and approximately 300,000 suffer from significant complications, including limb deformities, amputations, or other long-term effects. Regions like Sub-Saharan Africa, South Asia, Papua New Guinea, and Latin America are where venomous snakebites are a serious public health issue.
Today, January 15, a team spearheaded by researchers from the UW Medicine Institute for Protein Design and the Technical University of Denmark reported their findings regarding improved antivenom treatments in the journal Nature.
Susana Vazquez Torres, the primary author of the paper from the Department of Biochemistry at the UW School of Medicine, hails from Querétaro, Mexico, a region known for viper and rattlesnake populations. She aims to create innovative drugs to address neglected diseases, including snakebites.
The research team, which included international specialists in snakebite treatment and diagnostics, focused on developing methods to neutralize venom obtained from specific elapid snakes. Elapids, such as cobras and mambas, are a large family of venomous snakes found in tropical and subtropical areas.
Most elapid snakes possess two tiny fangs resembling shallow needles. During a sustained bite, the fangs inject toxins from glands located at the back of the snake’s mouth. Among these toxins are dangerous three-finger toxins that harm body tissues by killing cells and can lead to paralysis and death by disrupting nerve and muscle communication.
Currently, the treatment for bites from venomous elapid snakes involves using antibodies derived from the plasma of animals that have been immunized against the snake’s venom. Producing these antibodies is expensive, and they are only somewhat effective against three-finger toxins, often resulting in serious side effects such as shock or respiratory issues.
“The process of developing new treatments has been very slow and tedious,” remarked Vazquez Torres.
To accelerate the discovery of better therapies, the researchers employed deep learning techniques. They engineered novel proteins that interact with and mitigate the toxic and harmful effects of three-finger toxins by binding to them.
Through extensive experimental screenings, the team succeeded in designing proteins that displayed high thermal stability and strong binding affinity. The actual proteins synthesized in the lab matched the theoretical designs almost perfectly at the atomic level.
In laboratory tests, these engineered proteins successfully neutralized all three subfamilies of three-finger toxins. When administered to mice, the proteins provided protection against potentially fatal neurotoxin exposure.
The newly designed proteins offer significant benefits. They can be produced with consistent quality using recombinant DNA techniques, avoiding the need for animal immunization. (In this context, recombinant DNA technology refers to the lab methods used to translate the computational design of a new protein into a synthesized product.)
Furthermore, these proteins are smaller than traditional antibodies, potentially allowing for deeper tissue penetration to swiftly neutralize toxins and minimize damage.
In addition to paving the way for new antivenom development, researchers believe that computational design approaches could also be employed to create other antidotes. These methods may help identify treatments for underrepresented diseases that affect regions with limited scientific research capabilities.
“The use of computational design methods could greatly lower the costs and resources needed to develop treatments for neglected tropical diseases,” the researchers emphasized.
The senior researchers involved in designing protein treatments for elapid snakebites include Timothy J. Perkins from the Technical University of Denmark and David Baker from the UW Medicine Institute for Protein Design and the Howard Hughes Medical Institute. Baker holds a professorship in biochemistry at the UW School of Medicine.
The University of Washington has filed a provisional U.S. patent application for the design and formulation of the proteins developed in this study.
