Artificial intelligence could take the bite out of snake venom.
Using AI, scientists have designed proteins that say not so fassst to toxins wielded by cobras and other venomous snakes. It’s a proof-of-concept approach that could one day offer a new treatment for snakebites. In lab experiments, the custom proteins saved the lives of mice given an otherwise lethal dose of toxins , researchers report January 15 in Nature .
These proteins “are really doing their job,” says Michael Hust, an antibody researcher at the Technical University of Braunschweig in Germany who was not involved with the new research. “The mice are surviving. This is what we all want.”
The work represents the latest real-life application of work that earned three scientists the 2024 Nobel Prize in chemistry . In 2022, medical biotechnologist Timothy Jenkins spotted a preprint from the lab of David Baker, a biochemist at the University of Washington School of Medicine in Seattle and one of the Nobel awardees. The preprint described AI-designed proteins that stick like superglue to specific molecules .
That sparked an idea. Could the AI think up a design that clamps onto — and neutralizes — snake venom toxins?
Jenkins, of the Technical University of Denmark in Lyngby, had spent years trying to develop new therapies for snakebites. Worldwide, snakebites kill some 100,000 people each year. Venomous snakes can deliver a blizzard of toxins via their bite. Some of the most dangerous include molecules called three-finger toxins, which can paralyze muscles, stilling people’s hearts and their ability to breath. Antivenoms exist, but the technology is outdated, Jenkins says. “There’s not a lot of money in it, so not a lot of innovation has been attracted.”
Current antivenom producers milk snakes to extract their venom, which is “like handling a live hand grenade,” he says. A small dose of that venom gets injected into a horse or other large animal, from which producers later harvest antibodies.
When given to a snakebite victim, those antibodies bind to venom toxins and shut them down. But manufacturing antivenom is costly and time-consuming, so scientists have been searching for other methods. One option that’s seen recent success is scanning a vast collection of lab-made antibodies to identify those that target particular toxins .
With AI, scientists can quickly and cost-effectively build toxin-targeting proteins from scratch. Jenkins and Baker paired up to create custom proteins using a generative AI model called RFdiffusion. It’s a free protein-design tool that shares some similarity with the AIs that generate images. Instead of conjuring up a picture of the pope in a puffer jacket, RFdiffusion can concoct protein designs that match a molecule scientists want to target.
In the lab, human cells exposed to toxins from black-necked spitting cobra venom typically die off within about an hour and a half (left panel). Dying cells appear to light up like a pink Christmas tree. But treating the cells with designer proteins five minutes after toxin exposure fended off the lethal effects (right panel.) University of Washington Institute for Protein Design Baker’s team had previously trained the model on all known protein structures and their amino acid sequences, the string of molecular building blocks that fold up into a protein’s 3-D shape. Then, the researchers computationally disassembled those shapes. That taught the model how to put together a complete protein from its components, like learning how to build a car engine by taking it apart.
Baker and Jenkins asked the AI to design proteins that would glom on to venom toxins. Then they manufactured the proteins in the lab. Like a magnetic cap covering the tip of a key so it no longer fits in a lock, the synthesized proteins prevented the toxin from docking onto cells.
The team injected 20 mice with the custom proteins 15 minutes after a lethal dose of cobra toxins or concurrently with the toxins. Every mouse survived. “We were very, very excited about this,” Jenkins says. It was a stark demonstration of the proteins’ powers. Next, the team wants to develop its proteins into an actual product it could test in people. Scientists will need to ensure the custom proteins are safe, and not binding unexpectedly in human tissues, Hust says.
Jenkins agrees. The new study is just a first step to defanging venoms’ harms. “It was very much just proving that this extremely new technology works,” he says.
