The phylum Nemertea, commonly known as ribbon worms, comprises a diverse group of approximately 1350 species distributed worldwide, with the majority inhabiting marine environments. Predation and scavenging are the predominant feeding strategies observed among these species, facilitated by their eversible proboscis used for capturing prey. The secretions produced by Nemertea are known to contain a variety of toxins, including both low molecular weight compounds and protein/peptide-based cytolytic and neurotoxins. Despite their potential significance, research on nemertean toxins has been limited, with only a small fraction (approximately 5%) of known species having been investigated to any extent in this context [1].

In our recent studies [2] on epidermal secretions derived from Lineus longissimus, we discovered a novel family of peptide toxins which we named alpha-nemertides. One specific peptide, α-1, was subjected to detailed investigation. Comprising 31 residues, including two hydroxyprolines, and three disulfides forming an inhibitor cysteine knot motif within its peptide core. α-1 exhibited remarkable potency: it induced paralysis and death in green crabs (Carcinus maenas) at a dosage of approximately 300 pmol/kg, and selectively targeted invertebrate voltage-gated sodium channels at the low nanomolar range. Subsequent research expanded our understanding to encompass α-nemertides 2-7, as well as a series of 18 alanine mutants of α-1. Collectively, these studies provide valuable insights into the key residues responsible for modulating the activity and receptor subclass specificity of these peptides [3]. Furthermore, we extended our investigations to encompass a broader range of nemertean species, with a particular emphasis on the Lineidae lineage. This endeavour led to the discovery of an additional highly potent family of peptide toxins known as delta-nemertides. Here, we aim to present a comprehensive summary of our findings, while also discussing the potential applications, opportunities, and challenges associated with utilizing these toxins in the fields of medicine and agriculture.