Scientists have now used AI alongside computational protein design to develop snake antivenom, which blocks the lethal effects of snake venom.
Snake bites kill 100,000 people a year and have been declared a top-priority neglected tropical disease by the World Health Organization. The current treatment is an almost century-old method of immunizing horses and sheep with snake venom and then retrieving the antivenom produced in the serum. The antivenom produced has varying effects, and the technique has not improved either.
Computational protein design has enabled researchers to create custom proteins according to their requirements. American biochemist David Baker, who received the Nobel Prize for his fundamental contributions to the field, laid the groundwork for this technology. Now, bolstered by AI, custom proteins can be designed in seconds.
A member of Baker’s lab, biochemist Susana Vázquez Torres, saw an opportunity in Baker’s state-of-the-art computational protein design tool, RFdiffusion, to treat neglected diseases and snake bites. Snake venoms can cause paralysis and damage tissues, and if left untreated, it can cause death. These venoms are a cocktail of various protein toxins. Vázquez Torres, Baker and their colleagues used RFdiffusion to design ‘mini-binders’. These proteins recognize key regions of three kinds of toxins made by elapid snakes like cobras, adders, and mambas. The idea is to identify mini-binders that create strong bonds with the venomous protein components that contribute to the destruction of tissues and attack neurotransmitters present in nerves and muscles, inducing paralysis. The researchers did two experiments to prove how effective the AI-designed proteins are. In the first experiment, the scientists premixed the toxins with the antivenom and then injected the mixture into mice. None of the mice died in this experiment. To mimic an actual snake bite, the researchers injected the mice with lethal doses of venom, and 15 minutes later, the mini-binders were added, and in this case, the animals survived.
The antivenoms developed are promising, but it is still a far-fetched idea to consider it a potent treatment for snake bites. However, some positives go in favor of this novel treatment. Firstly, the mini-binders are more stable than the current antivenoms, which will potentially scratch off the need for refrigeration. The antivenoms can also be churned out at low cost through fermentation by bacteria.
However, the designed antivenoms have not yet been studied, nor have they been proven to have a broad spectrum since the treatment has been tested only against venoms of elapids.
The next goal for Vázquez Torres and Baker’s lab is to move the antivenoms to the clinic. As for Vázquez Torres, she thinks that the final product will be a mix of different mini-binders, which would depend on the species of snakes found in the concerned area.
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