Biodiversity of the genus Conus (Fleming, 1822): A rich source of bioactive peptides

In this paper, we present an overview of the biodiversity of both marine snails of the large genus Conus and their venoms. After a brief survey of Conidae malacology, we focus on the high degree of biodiversity of this genus, its specific biogeography as well as its habitat, and the relatively strict diet of its members. The venom of Conidae species contains a large number of peptides that can interact selectively with key elements of the peripheral and central nervous systems of vertebrates and invertebrates. Emphasis is on summarizing our current knowledge of the specific actions of venom components on ionic channels, receptors and other key elements of cellular communication. The peptides isolated from venoms, called conotoxins, form different families according to both their primary structure and their specific pharmacological targets. Three families encompassing the mu-, mu O- and delta-conotoxins target voltage-sensitive sodium channels but with different modes of action or tissue selectivity. Another important class of conotoxins is the omega-conotoxin family which acts on voltage-sensitive calcium channels. The alpha-conotoxin family is represented by several peptides blocking muscular or neuronal nicotinic acetylcholine receptors. Finally a blocker of potassium channels is presented as well as two conotoxins acting on the N-Methyl-D-Aspartate receptor. Primary structures and cysteine frameworks of all these conotoxins are shown and compared. At the end of the review, we report the contribution of molecular biology to identification of new conotoxins having original pharmacological properties. In conclusion, conotoxins have received increasing attention from physiologists, pharmacologists, biochemists and physicians because of their selectivity as well as their pharmacological and therapeutic potential.