# Innovatively Crafted AI-Driven Proteins Present Promise for Combating Lethal Snake Venoms
Snakebites continue to be an unspoken threat worldwide, particularly impacting economically disadvantaged areas. Annually, over two million individuals suffer snake bites, leading to more than 100,000 fatalities and 300,000 people facing permanent disabilities. Although conventional antivenoms are life-saving, they come with significant limitations: outdated manufacturing methods, high costs, and a necessity for refrigeration, in addition to having a restricted effectiveness against certain venom components.
Nevertheless, an innovative strategy that merges deep learning with synthetic biology is set to transform this domain. New, bespoke proteins designed to counteract some of the most deadly snake venom toxins have been created. These advanced solutions promise stability, affordability, and simpler production compared to standard antivenoms—and could significantly impact addressing snakebite envenomation in resource-constrained regions.
## **The Challenge of Snake Envenomation**
Snakebites primarily impact individuals in rural tropical zones of nations like India, sub-Saharan Africa, and Southeast Asia. In these regions, access to antivenoms is often hampered by logistical hurdles and the steep price of conventional antivenom treatments. Snake venoms consist of intricate mixtures of toxins, causing effects that include tissue destruction, paralysis, organ failure, and potential death. Many of the most venomous snakes globally—such as cobras, mambas, and kraits—produce three-finger toxins, small, stable proteins that contribute significantly to the severity of their venoms.
Current methods for producing antivenoms are outdated and depend on animal immunization. According to Timothy Jenkins, a medical biotechnologist from the Technical University of Denmark, “You take the venom of interest, inject it into a horse, and wait for about a year for the immune system to produce antibodies for this tiny amount of venom.” These antibodies obtained from horses are then collected, purified, and made into antivenom. However, this process presents several serious drawbacks: it is lengthy, costly, and frequently results in antivenoms that inadequately neutralize specific toxins such as three-finger proteins.
## **A Cutting-Edge Approach: Merging Protein Design and AI**
To address the constraints of traditional antivenoms, researchers led by Nobel laureate David Baker at the University of Washington in Seattle, in conjunction with Jenkins and a global team, aimed to create customized proteins that neutralize venom toxins. Their research, propelled by advanced deep learning and artificial intelligence (AI), marks a new era in biomedicine.
The team used a well-known AI-driven protein design process developed in Baker’s lab. As computational biotechnologist Susana Vázquez Torres explains, the initial phase involved selecting specific venom toxins as targets, like three-finger toxins. “The algorithm investigates various protein structures that will bind to it,” she says. This technique effectively reverse-engineers proteins capable of attaching to the venom molecules with great accuracy.
Employing a secondary program, they enhanced these designs by choosing amino acid sequences that would improve protein-target attachment. They then utilized DeepMind’s groundbreaking AlphaFold tool to predict which protein designs had the highest likelihood of achieving functional, stable formations. By evaluating hundreds of thousands of candidates through machine learning, the team ultimately synthesized the most promising designs for real-world evaluation.
The outcome? A collection of “de novo” proteins—novel proteins not found in nature—that can neutralize three-finger toxins. In contrast to natural antibodies, these diminutive protein molecules demonstrate thermal stability, low production costs, and durability against environmental factors, making them perfectly suited for deployment in remote or resource-limited areas.
## **Mechanism of Action of These Synthetic Proteins**
The designer proteins function by firmly binding to the three-finger toxin molecules. For neurotoxic three-finger toxins, the proteins serve as molecular decoys, obstructing the toxins’ capability to attach to their target sites on nerve cells, thereby averting paralysis. Regarding cytotoxic three-finger toxins that damage cell membranes and induce tissue necrosis, the researchers went further by designing proteins with unique shapes that envelop the tips of the cytotoxins, effectively protecting victims from their lethal impacts.
This novel strategy targets toxins with exceptional specificity, surpassing traditional antivenoms in various aspects. The resulting proteins are not only thermally stable and easier to produce, but they also maintain their efficacy even when administered up to 30 minutes after toxin exposure—a crucial timeframe for treating envenomated individuals in the field.
## **Encouraging Laboratory Findings**
In trials involving animals, the synthetic proteins exhibited remarkable efficacy. For instance, when mice were injected with cobra venom, the designer proteins neutralized the venom’s toxicity even with a 30-minute delay in administration. “We had very low amounts of our therapeutic agent completely neutralize toxicity,” Jenkins emphasizes. These findings highlight the potential of this innovative approach.