Sea snail venom offers possibilities of designing human ailments drugs

In a first of its kind study, peptides, from the venom of cone snails, have been identified that opens up possibilities of drug research for several human ailments.

The study was conducted by a team of Indian scientists from Port Blair-based National Institute of Ocean Technology, NIOT and Indian Institute of Science, IISc, Bangalore.

They identified short peptides with six amino acids, which globally, is the first small contryphan identified so far.

The abstract of the study says, "We identified 12 short single disulfide-containing conopeptides from the venom of Conus coronatus, C. leopardus, C. lividus and C. zonatus. Interestingly, we detected the shortest contryphan sequence thus far characterized which contains only six amino acid residues. We also identified three distinct contryphan sequences of C. lividus without any proline residues and one sequence with an unusual post-translational modification (bromination of tryptophan). Furthermore, we characterized venom peptides of C. zonatus for the first time."

"Conopeptides are now widely used in experimental neuroscience, and a few peptides have been developed for diagnostic and therapeutic applications. Conopeptides have high specificity and potency in both the medical as well as applications in basic neuroscience research," told lead author of the study Dr J. Benjamin Franklin, scientist at NIOT, to Indian Science Journal.

Specimens of cone snails were collected from the Andaman and Nicobar Islands. The venom of predatory marine cone snails mainly contains a diverse array of unique bioactive peptides, commonly referred to as Conopeptides.

These peptides have proven to be valuable pharmacological probes and potential drugs, because of their high specificity and affinity for important ion channels, receptors and transporters of the nervous system.

Venom peptides target a wide variety of membrane-bound protein channels and receptors. A number of these peptides have been used in vivo for proof-of-concept studies. Several venom peptides have undergone pre-clinical or clinical development for the treatment of pain, diabetes, multiple sclerosis and cardiovascular diseases.

Dr Franklin admitted the team has not done anything on the application side of the short peptides presently identified.

He, however, added that they plan to work on the functional aspects of these short peptides. Given the accelerated pace at which different peptides from the cone snail venoms are being elucidated, it is certain that the use of these pharmacological agents as tools for the neuroscientist will continue to increase in the near future.

There are more than 700 different species of cone snails in the world. Most of them are found in subtropical areas of the Atlantic, Indian, and Pacific oceans with a majority of them in the tropical waters of the Indo-Pacific Ocean. These snails live in shallow waters ranging from tidal flats down to depths of several hundred meters in various microhabitats.

Many of the species are associated with the coral reefs, under coral heads, while some prefer sand, mud, rock or coral rubble substrates. Cone snails generally eat marine worms, small fish, and even other molluscs immobilizing them with unique venoms. Because of their slow moving capability, cone snails use a venomous harpoon (radula) to catch fast-moving prey such as fish.

The venom of some species, especially fish eating cones are powerful enough to kill human beings. But, members of the family Conidae, do not predate upon humans, but will sting if disturbed. Many such incidents in Pacific waters have been reported. The cone snails are predacious and feed on preys, injecting venom by means of a detachable spear-shaped radular tooth, based on a high-speed ballistic prime and shoot mechanism. This is one of the fastest known methods of prey catching and has a time course similar to that of the trap jaw response (0.33 to 1milliseconds) of the ant Odontomachus.

Dr Franklin works on diversity, distribution, teeth morphology, biogeography, phylogeny and venom peptides of Indian cone snails for the past 14 years and presently working at the Andaman and Nicobar Centre for Ocean Science and Technology, National Institute of Ocean Technology, Port Blair.

His joint author Dr R.P. Rajesh works on peptide chemistry and genomics of cone snail venom at Molecular Biophysics Unit at IISc.

The study was published in Toxicon, an interdisciplinary journal on toxins derived from animals, plants and microorganisms.