Chapter Eight - Methods for Deployment of Spider Venom Peptides as Bioinsecticides

Abstract

Despite intensive control measures, insect pests cause enormous damage to crops and stored grain. In addition, insects vector some of the world's most devastating human diseases, including malaria, dengue and Chagas disease. Chemical insecticides remain the dominant method of controlling insect pests but the arsenal of extant insecticides is rapidly diminishing due to the evolution of resistance in pest species and a more difficult regulatory environment due to heightened concern about the potential adverse impacts of chemical insecticides on human health and the environment. Along with predatory beetles, spiders are the most successful insect predators on the planet and their venoms contain a diverse array of small, disulfide-rich insecticidal peptides. In addition to being potent and highly selective for insects, they collectively offer very diverse pharmacology and should degrade to innocuous breakdown products in the field. However, their major disadvantage is a low level of intrinsic oral activity. Consequently, much research has been directed towards improving the oral activity of these peptide toxins or, alternatively, obviating the oral activity problem altogether by incorporating transgenes encoding the toxins into suitable biological delivery vehicles. Here, we discuss recent advances in both of these areas. We also discuss an approach that merges the advantages of small-molecule and peptide-based insecticides, namely using the pharmacophore of an insecticidal spider-venom peptide to rationally develop a small-molecule mimetic that has improved oral activity, but retains activity for a novel insecticide target.