From Mollusks to Medicine: A Venomics Approach for the Discovery and Characterization of Therapeutics from Terebridae Peptide Toxins

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 Molecular Basis of Toxins’ Interactions with Intracellular Signaling via Discrete Portals

“…Thus, in answer to the question posed above, we would like to propose that although there is a remarkable diversity between these portals , they are tightly linked to the amplification attained by the relatively limited cellular signaling transduction cascades. The recent development of venomics [446], toxins proteomics and genomics may facilitate rapid screenings for toxicity of molecules acting on this signal transduction machinery [447,448], based on safety as well as efficacy, thereby providing solid grounds for better drug discovery and translational medicine [449]. …”

Tick Bioactive Molecules as Novel Therapeutics: Beyond Vaccine Targets

“…Such studies have led to the discovery of many new promising therapeutic candidates, such as animal venom peptides from mollusks (Verdes et al, 2016) and antibiotics from bacteria (Wecke and Mascher, 2011). …”

A Graph-Directed Approach for Creation of a Homology Modeling Library: Application to Venom Structure Prediction

“…Toxins have for a long time been considered a rich natural source of therapeutic leads because of their high specificity and binding affinity for various receptors involved in different biological pathways [Zambelli et al, 2016, Verdes et al, 2016. The drug ziconotide, for example, is a potent analgesic derived from a toxin produced by the aquatic cone snail species Conus magus [Miljanich, 2004].…”