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There are over 15,000 species of conoideans, with an estimated venom-peptide reservoir of over a million compounds 19. Additionally, the compact size of conoidean venom peptides and their enhanced disulfide-bridged stability make them good candidates for pharmaceutical drug discovery and development 17, 18. Cone snail venom peptides have shown remarkable selectivity for their molecular target, ion channels and receptors 14, 15, 16. Predatory marine snails of the conoidean family, which includes cone snails (Conidae), terebrids (Terebridae), and turrids (Turridae), use venom peptides to prey on fish, worms, and other mollusks 6, 11, 13. There is a need for new whole-animal in vivo methods that are applicable to scant quantities of venom peptides.Ī striking example of the discovery-to-function gap in venom peptides is the identification and characterization of peptides from marine snail venom. Lacking from these is the ability to efficiently characterize the physiological properties of the enormous diversity of venom peptides being identified. A variety of high-throughput electrophysiology, fluorescence, and radioactivity-based bioassays have been used to accelerate characterization of novel venom peptides 12. However, translating newly discovered venom peptides into commercial therapeutics is challenging 11.

Venom-peptide research and drug discovery has increased exponentially with the advance of genomic–transcriptomic sequencing and proteomic mass-spectrometry 10. Currently, six venom-derived peptides are commercially available drugs: ziconotide for pain 5 exenatide for diabetes 6 bivalirudin for anticoagulation 7 captopril for hypertension 8 and eptifibatide and tirofiban for coronary syndrome 9.

Specifically, venoms contain numerous, diverse peptides, many with highly specific bioactive properties that have proven useful as pharmacological therapeutics 2, 3, 4.

Due to the energetic cost of venom and the need for a fast-acting biological effect, venoms have evolved into cocktails of molecules with potent neurotoxic, haemophilic, and cytotoxic activities 1. Venomous animals use their expansive venom arsenal to disrupt the physiology of other animals for both defensive and predatory purposes. Tv1 and Tsu1.1 are distinct from previously identified venom peptides, expanding the toolkit of peptides that can potentially be used to investigate the physiological mechanisms of pain and diet. These findings describe the first functional bioactivity of terebrid venom peptides in relation to pain and diet and indicate that Tv1 and Tsu1.1 may, respectively, act as antinociceptive and orexigenic agents. Alternatively, Tsu1.1 (100 µM) increased food intake. Tv1 (100 µM) had an antinociceptive effect in adult Drosophila using a thermal nociception assay to measure heat avoidance. Our results indicate that Tv1 and Tsu1.1 have distinct bioactivity. Using this approach, we characterized the physiological and behavioral phenotypes of two peptides from the venom of predatory terebrid marine snails, teretoxins Tv1 from Terebra variegata and Tsu1.1 from Terebra subulata. To address this discovery-to-function gap, we developed a sequence driven:activity-based hybrid approach for screening venom peptides that is amenable to large-venom peptide libraries with minimal amounts of peptide. There is a pressing need for a systematic, cost effective, and scalable approach to identify physiological effects of venom peptides. The number of newly discovered peptides from the transcriptomes and proteomes of animal venom arsenals is rapidly increasing, resulting in an abundance of uncharacterized peptides.

Che over tub lid without adding screen snake