No abstract

Throughout evolution, numerous proteins have been convergently recruited into the venoms of various animals, including centipedes, cephalopods, cone snails, fish, insects (several independent venom systems), platypus, scorpions, shrews, spiders, toxicoferan reptiles (lizards and snakes), and sea anemones. The protein scaffolds utilized convergently have included AVIT/colipase/prokineticin, CAP, chitinase, cystatin, defensins, hyaluronidase, Kunitz, lectin, lipocalin, natriuretic peptide, peptidase S1, phospholipase A 2 , sphingomyelinase D, and SPRY. Many of these same venom protein types have also been convergently recruited for use in the hematophagous gland secretions of invertebrates (e.g., fleas, leeches, kissing bugs, mosquitoes, and ticks) and vertebrates (e.g., vampire bats). Here, we discuss a number of overarching structural, functional, and evolutionary generalities of the protein families from which these toxins have been frequently recruited and propose a revised and expanded working definition for venom. Given the large number of striking similarities between the protein compositions of conventional venoms and hematophagous secretions, we argue that the latter should also fall under the same definition. 483

Key technical advances in combination with a renewed industry-wide focus on biologics have converged to provide a larger than ever pipeline of venom-derived therapeutics. Disulfide-rich venom peptides obviate some of the traditional disadvantages of therapeutic peptides and some may be suitable for oral administration. Moreover, some venom peptides can breach the blood brain barrier and translocate across cell membranes, which opens up the possibility of exploiting molecular targets not previously accessible to peptide drugs.

Spider venoms are an incredibly rich source of disulfide-rich insecticidal peptides that have been tuned over millions of years to target a wide range of receptors and ion channels in the insect nervous system. These peptides can act individually, or as part of larger toxin cabals, to rapidly immobilize envenomated prey owing to their debilitating effects on nervous system function. Most of these peptides contain a unique arrangement of disulfide bonds that provides them with extreme resistance to proteases. As a result, these peptides are highly stable in the insect gut and hemolymph and many of them are orally active. Thus, spider-venom peptides can be used as stand-alone bioinsecticides, or transgenes encoding these peptides can be used to engineer insect-resistant crops or enhanced entomopathogens. We critically review the potential of spider-venom peptides to control insect pests and highlight their advantages and disadvantages compared with conventional chemical insecticides.