Venom, Peptides, and Biomedical Research

It may seem far-fetched that lethal venom can provide healing solutions, but the biochemistry behind Killer Snails: Assassins of the Sea is real. In fact, characterizing, or identifying, venom peptides is an area of active research.

A peptide is a molecule that consists of amino acids linked in a chain. Smaller than proteins, peptides are biomolecules that, due to their structure and high target affinity, may be exploited for therapeutic drug development.

Connecting Evolution and Drug Discovery

Over the course of evolutionary history, the peptide toxins found in cone snail venom have been optimized to instantly disable the prey's nervous system. The highly efficient and specific nature of the cone snail's venom "cocktail" may provide new insights to biological pathways that can be useful to medicine. Combining evolutionary studies and drug discovery research can enhance knowledge in both areas.

Venom Science In-Depth

For detailed scientific discussions on venomics and evolution, see the following presentations and papers:

Presentations

 

Biochemist Mandë Holford, an expert in snail venom, speaks at the World Economic Forum: Annual Meeting of New Champions. Her lab at Hunter College-City University of New York and The American Museum of Natural History, is taking inspiration from nature to turn venoms into potential cures.

 

Abstract: Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1) delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2) identification and classification of putative teretoxins through omics methodologies, including genomics, transcriptomics, and proteomics; (3) chemical and recombinant synthesis of promising peptide toxins; (4) structural characterization through experimental and computational methods; (5) determination of teretoxin bioactivity and molecular function through biological assays and computational modeling; (6) optimization of peptide toxin affinity and selectivity to molecular target; and (7) development of strategies for effective delivery of venom peptide therapeutics. While our research focuses on terebrids, the venomics approach outlined here can be applied to the discovery and characterization of peptide toxins from any venomous taxa.

The Terebridae and teretoxins: Combining phylogeny and anatomy for concerted discovery of bioactive compounds

Abstract: The Conoidea superfamily, comprised of cone snails, terebrids, and turrids, is an exceptionally promising group for the discovery of natural peptide toxins. The potential of conoidean toxins has been realized with the distribution of the first Conus (cone snail) drug, Prialt (ziconotide), an analgesic used to alleviate chronic pain in HIV and cancer patients. Cone snail toxins (conotoxins) are highly variable, a consequence of a high mutation rate associated to duplication events and positive selection. As Conus and terebrids diverged in the early Paleocene, the toxins from terebrids (teretoxins) may demonstrate highly divergent and unique functionalities.

 

Abstract: Disulfide-rich peptide toxins found in the secretions of venomous organisms such as snakes, spiders, scorpions, leeches, and marine snails are highly efficient and effective tools for novel therapeutic drug development. Venom peptide toxins have been used extensively to characterize ion channels in the nervous system and platelet aggregation in haemostatic systems.

 

Abstract: Venom peptides from predatory organisms are a resource for investigating evolutionary processes such as adaptive radiation or diversification, and exemplify promising targets for biomedical drug development. Terebridae are an understudied lineage of conoidean snails, which also includes cone snails and turrids. Characterization of cone snail venom peptides, conotoxins, has revealed a cocktail of bioactive compounds used to investigate physiological cellular function, predator-prey interactions, and to develop novel therapeutics.