Chapter 8: Therapeutic Applications of Spider-Venom Peptides

Spiders are the most speciose venomous animals and, along with predatory beetles, the most successful terrestrial predators. The 45 000 spider species described to date probably represent less than half the taxonomic diversity of these arachnids. If one uses conservative estimates of 50 000 species and 200 peptides/venom, then spider venoms are likely to contain at least 10 million bioactive peptides. The venom peptidome of spiders is dominated by peptides containing an inhibitor cystine knot motif, which endows these peptides with exceptional resistance to extremes of pH, organic solvents, high temperatures, and proteases. Although no therapeutics have yet been derived from spider venoms, the most potent modulators of several “hot” therapeutic targets such as transient receptor potential channels, voltage-gated sodium channels, and acid-sensing ion channels are spider-venom peptides. In this chapter we survey the chemistry and pharmacology of spider venoms with a focus on the biological activities that are most relevant for therapeutic development. We also provide an in-depth analysis of spider-venom components that have been patented for medical applications and discuss their potential as a source of drugs.