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

Biochem Pharmacol. 2020 Nov:181:114107. doi: 10.1016/j.bcp.2020.114107. Epub 2020 Jun 21.

Abstract

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 (NaV), calcium (CaV), and potassium (KV) channels. Spider venoms, in particular, contain potent and selective peptides targeting these channels, with a few displaying interesting multi-target properties for NaV and CaV 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 NaV and CaV channels. This perspective discusses spider venom peptides displaying multi-target properties to modulate NaV and CaV 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.

Keywords: Diseases; Ion channels; Multi-target; Spider venom; Therapies; Venom peptides.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / therapeutic use*
  • Humans
  • Molecular Targeted Therapy / methods
  • Motor Neuron Disease / drug therapy*
  • Motor Neuron Disease / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neuralgia / drug therapy*
  • Neuralgia / metabolism
  • Peptides / chemistry
  • Peptides / therapeutic use*
  • Sodium Channel Blockers / chemistry
  • Sodium Channel Blockers / therapeutic use*
  • Venoms / chemistry
  • Venoms / metabolism

Substances

  • Calcium Channel Blockers
  • Peptides
  • Sodium Channel Blockers
  • Venoms