Development of a powerful antidote against lethal neurotoxic snakebites using the naturally occurring acetylcholine binding protein (AChBP) as a decoy receptor.

The world’s 1.8 million snakebite victims (~138,000 deaths per year) are currently treated with antibodies derived from hyperimmune equine/ovine serum, known as antivenom. Although these treatments save tens of thousands of lives each year, they have numerous limitations. They have laborious and expensive production and a high incidence of severe adverse effects associated with them. Most of these side effects are associated with the immunogenicity of the antisera. Both anaphylactic and delayed reactions (serum sickness) occur. In addition, antivenoms have poor specificity, with only 10-20% of the antibodies being specific to the snake venom toxins used as immunogens. Moreover, they usually have very poor cross-reactivity against the venoms found in other snake species, even within the same family or genus, due to venom toxin variation. This makes manufacturing a single therapy for a large geographical region extremely problematic. We aim to overcome all of these limitations using an engineered acetylcholine binding protein (AChBP), which acts as a universal decoy receptor for snake neurotoxins.

Keywords:Neuroscience, Neglected tropical diseases, Protein design, Nicotinic acetylcholine receptor, X-ray crystallography

Disciplines:Toxinology