According to the WHO, venomous snakebites affect between 1,8 and 2,7 million people each year, leading to roughly 100,000 annual deaths and three times as many permanent disabilities, including lost limbs. Most injuries happen in Africa, Asia, and Latin America, where weak health systems aggravate the issue.
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 in the paper De novo designed proteins neutralize lethal snake venom toxins, publishedon 15 January in Nature.
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 Bioengineering used deep learning tools to design new proteins that bind to and neutralise toxins from deadly cobras.
80-100% survival rate in mice
The study focuses on an important class of snake proteins called three-finger toxins, often the reason antivenoms based on immunised 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 neutralise 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 immunisation 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 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 neutralise 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."
Novel approach to drug development
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,” says David Baker.
