Snake venoms are an incredible example of evolution where many ecologically distinct species developed their own unique toxin profile to aide their niche. Against humans, these venoms can lead to hemotoxic, neurotoxic and tissue damaging effects leading to the mortality of over 100,000 people each year. Identifying and characterising the mechanisms by which these venoms alter human physiology can lead to the identification of novel therapeutics to treat envenoming.
To better understand how snake venoms act at the molecular level, we employed whole genome CRISPR knockout (KO) screening. We focus our efforts here on the puff Adder (B. arietans), a snake associated with one of the greatest morbidity across central and northern Africa. From this, we have identified several molecular targets this venom uses to exert their cytotoxic effects. Of note, N-cadherin (CDH2); a cell adhesion protein was required for the cytotoxic effects of several evolutionary distinct vipers; We continue to characterise these molecular interactions, with the goal of developing new rational venom antidotes for common venom/ host targets.