Insect toxins – selective pharmacological tools and drug/chemical leads

Abstract

Insect toxins comprise a diverse array of chemicals ranging from small molecules, polyamines and peptide toxins. Many target nervous system and neuromuscular ion channels and so rapidly affect the behaviour of animals to which the toxin is applied or injected. Other modes of action have also been identified. Wasps, bees, flies, beetles and ants generate a rich arsenal of channel-active toxins, some of which offer selective pharmacological probes that target particular ion channels, while others act on more than one type of channel. Philanthotoxins from the digger wasp have been fruitful in adding to our understanding of ligand-gated ion channels in the nervous system and at neuromuscular junctions. Fire ants produce the toxic alkaloid solenopsin, a molecule which has stimulated attempts to generate synthetic compounds with insecticidal activity. Apamin from bee venom targets calcium-activated potassium channels which can in turn control the release of neuropeptides. Melittin, another bee venom component, is a membrane-acting peptide. The saliva of the assassin bug contains toxins that target the voltage-gated calcium channels of their insect prey. Certain beetles produce diamphotoxin, a haemolytic peptide toxin with traditional use as an arrow poison and others generate leptinotarsin with similar properties. Mastoparan is a powerful peptide toxin from wasp venom. Its toxic actions can be engineered out leaving a potent antimicrobial molecule of interest. Here we describe the modes of action of such compounds and evaluate their potential as neuroactive pharmacological tools and candidate lead molecules for insect control and as therapeutic candidates with potential antimicrobial, antiviral and anti-cancer applications.

Tying pest insects in knots: the deployment of spider‐venom‐derived knottins as bioinsecticides

“…Moreover, most spiders are generalist predators, and are therefore adept at killing both pollinators and natural predators of pest insects, making them unsuitable for biocontrol. However, this does not discount the possibility that individual insecticidal toxins found in the venom of spiders might have application in the control of insect pests …”

“…However, this does not discount the possibility that individual insecticidal toxins found in the venom of spiders might have application in the control of insect pests. 4,[9][10][11]…”

Strategies towards Targeting Gαi/s Proteins: Scanning of Protein‐Protein Interaction Sites To Overcome Inaccessibility

“…Prominent members of this group are the wasp venom 14mer peptide mastoparan (H‐INLKALAALAKKIL‐NH 2 ) and the bee venom 26mer peptide melittin (H‐GIGAVLKVLTTGLPALISWIKRKRQQ‐NH 2 ). Both venom toxins are able to disrupt cell membrane phospholipids and to cause lysis [131,136–139] …”

An overview of the bioactive compounds, therapeutic properties and toxic effects of apitoxin

“…The mechanism underlying toxicity is based in the disruption of phospholipid bilayers which lead to mast cells' lysis and the release of compounds like lysosomal enzymes, histamine and serotonin, triggering pain and inflammation. Therefore, MLT together with hyaluronidase and PLA 2 , are responsible for venom allergenic properties breaking up membranes cells and enhancing their cytotoxic effect (Kachel et al, 2018).…”