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. Recent analyses of the Terebridae, a largely distributed family with more than 300 described species, indicate they have evolutionary and pharmacological potential. Based on a three gene (COI, 12S and 16S) molecular phylogeny, including ~50 species from the West-Pacific, five main terebrid lineages were discriminated: two of these lineages independently lost their venom apparatus, and one venomous lineage was previously unknown. Knowing the phylogenetic relationships within the Terebridae aids in effectively targeting divergent lineages with novel peptide toxins. Preliminary results indicate that teretoxins are similar in structure and composition to conotoxins, suggesting teretoxins are an attractive line of research to discover and develop new therapeutics that target ion channels and receptors. Using conotoxins as a guideline, and innovative natural products discovery strategies, such as the Concerted Discovery Strategy, the potential of the Terebridae and their toxins are explored as a pioneering pharmacological resource.
Highlights
The conoideans are a hyperdiverse group of marine gastropods that prey on fish, worms, and other mollusks (Figure 1)
Several conoidean lineages are characterized by specialized organs referred to as a venom apparatus that is used to subdue prey [1]
Similar to cone snails terebrids possess venom peptide toxins that appear rich in variety and functional applications (Table 1)
Summary
The conoideans (cone snails, terebrids, and turrids) are a hyperdiverse group of marine gastropods that prey on fish, worms, and other mollusks (Figure 1). Analysis over the last three decades of venom toxins produced by various species in the genus Conus (cone snails), the most famous representative of this group, reveal a complex system of molecular compounds Most of the main lineages of conoideans, including terebrids and conids, diverged at least in the early Paleocene [8] Such an early separation would indicate toxins from terebrids could be highly divergent and unique, compare to toxins found in the genus Conus. Recent results highlight the advantage of CDS to quickly define independent lineages within Conus [9,10] and the terebrids [11,12], facilitating the identification of numerous and divergent species, each producing unique peptide toxins. By analogy with “conotoxin”, the term “teretoxin” is introduced to designate natural peptide toxins produced by terebrid snails
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