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ARTICLE | Distillery Therapeutics

De novo-designed antivenom for snakebite

January 28, 2025 12:54 AM UTC

Computationally designed protein antivenoms could help treat snake bite envenoming by elapid snakes, which includes the Naja genus commonly known as cobras, by neutralizing all three subfamilies of the snakes' three finger toxins: short- and long-chain α-neurotoxins, and cytotoxins.

Diffusion model-based computational design of proteins to block binding of α-neurotoxins to the neurotransmitter receptor nAChR, followed by in vitro screening of the top 44 candidates using yeast surface display, yielded a candidate that bound a consensus short-chain neurotoxin with a Kd of 42 nM. Further optimization via computational design yielded an antivenom protein that bound the consensus toxin with a Kd of 0.7 or 0.9 nM, depending on the method of measuring. ...

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