Multi-targeting sodium and calcium channels using venom peptides for the treatment of complex ion channels-related...

Venom peptides are amongst the most exquisite group of bioactive molecules able to alter the normal physiology of organisms. These bioactive peptides penetrate tissues and blood vessels to encounter a number of receptors and ion channels to which they bind with high affinity and execute modulatory activities. Arachnid is the most diverse class of venomous animals often rich in peptides modulating voltage-gated sodium (Na_V), calcium (Ca_V), and potassium (K_V) channels. Spider venoms, in particular, contain potent and selective peptides targeting these channels, with a few displaying interesting multi-target properties for Na_V and Ca_V channels underlying disease mechanisms such as in neuropathic pain, motor neuron disease and cancer. The elucidation of the pharmacology and structure-function properties of these venom peptides are invaluable for the development of effective drugs targeting Na_V and Ca_V channels. This perspective discusses spider venom peptides displaying multi-target properties to modulate Na_V and Ca_V channels in regard to their pharmacological features, structure-function relationships and potential to become the next generation of effective drugs to treat neurological disorders and other multi-ion channels related diseases.