Conus Venoms - A Rich Source of Peptide-Based Therapeutics

Abstract

Over two decades of research on venom peptides derived from cone snails ("conopeptides or conotoxins") has led to several compounds that have reached human clinical trials, most of them for the treatment of pain. Remarkably, none of the conopeptides in clinical development mediate analgesia through the opioid receptors, underlying the diverse and novel neuropharmacology evolved by Conus snails. These predatory animals produce an estimated approximately 100,000 distinct conotoxins, a vast majority yet to be discovered and characterized. The conopeptides studied to-date in animal models, have exhibited antinociceptive, antiepileptic, neuroprotective or cardioprotective activities. Screening results also suggest applications of conotoxins in cancer, neuromuscular and psychiatric disorders. Additional potentially important applications of conotoxin research are the discovery and validation of new therapeutic targets, also defining novel binding sites on already validated molecular targets. As the structural and functional diversity of conotoxins is being investigated, the Conus venoms continue to surprise with the plethora of neuropharmacological compounds and potential new therapeutics. This review summarizes recent efforts in the discovery of conopeptides, and their preclinical and clinical development.

Identifying Key Amino Acid Residues That Affect α-Conotoxin AuIB Inhibition of α3β4 Nicotinic Acetylcholine Receptors

“…Peptides isolated from the venom of cone snails belonging to the genus Conus are valuable pharmacological tools, and some are also promising drug leads (1)(2)(3)(4)(5). ␣-Conotoxins are a subfamily of these peptides and consist of 12-19 amino acid residues, including four cysteines with a characteristic CC-C-C arrangement (type I cysteine framework) (6,7).…”

Centipede venoms as a source of drug leads

“…Many more venom-derived molecules that target an even wider range of disorders, including autoimmune disease, stroke and cancer, are in clinical and preclinical development [2][3][4][5][6][7][8][9][10]. Most of these molecules were derived from just a few well-studied venomous taxa [5,11], and therefore venoms remain an underutilized source of pharmacologically active compounds.…”

In silico study of peptide inhibitors against BACE 1

“…In the past, therapeutic peptides have been found in a variety of unexpected animal and plant sources ranging from venom of cone snails (Han et al 2008), spiders (Saez et al 2010;Gui et al 2014) to sea anemones (Rodríguez et al 2014). Genetic or recombinant libraries and chemical libraries (Meloen et al 2004) have also been the source of therapeutic peptides and synthetic combinatorial libraries have been used to identify bioactive peptides (Falciani et al 2005).…”