Ion channel tools and therapeutics from venoms and toxins

For almost as long as the ion channels in our brains have powered conscious thought, we have been fascinated by venoms and toxins. Initially thought of as magical, now we are understanding their true power and utility in drug discovery. A diverse range of venoms and toxins have been used to decipher the properties of ion channels and as a result hold a key functional place as positive controls in many assays. Such control toxins include tetrodotoxin, protoxin and charybdotoxin that are found in diverse species. The latest advances in computational chemistry and structural biology, such as cryogenic electron microscopy and free energy perturbation, are opening our drug discovery gaze to the atomic interactions of toxins and ion channels. Coupled with advances in ion channel screening and peptide biochemistry, we are on the verge of a new wave of toxin discovery and clinical application. These toxins also tackle challenging drug targets that are in desperate need of new chemical modalities. This chapter details the advances in toxin drug discovery though clinical development and new understanding of licensed drugs that feeds back to improve further therapeutic opportunities.