Sunday, December 18 2005 10:42 Hrs (IST) - World Time -

Mumbai: India could become a leader in supply of pain relieving drugs, including new anaesthetic compounds, if the vast potential of the country's natural colorful marine cone snails are tapped for their novel peptides.

The beautifully colored cone snails have the most highly structured small peptides which are the major toxic constituents of their venoms, a family of widely-distributed predatory marine mollusks, says Dr K S Krishnan of National Centre for Biological Studies of the Tata Insititute of Fundamental Research (NCBS-TIFR) said.

"These toxic components of cone snail venoms are becoming increasingly popular as tools for neuroscience research and drug discovery," he said.

"New and effective pain killers and anaesthetic compounds are promised for the world and India has also joined a select number of laboratories mainly from the US, Europe, Australia, Israel, and China which are engaged in intense drug discovery programmes based on peptides from a few snail species," he added.

Recently, the NCBS-TIFR has begun an extensive study on these cones found along the southeastern Indian coast and has already shown signs of promise as the scientists could isolate more than 40 bioactive peptides from nine species of the genus Conus.

It is estimated that coastal India has about 20-30 per cent of nearly 500 cone species known.

"We have lot of scope in drug development especially pain killers which are most sought-after drugs in the world for all kinds of pain," Krishnan said.

The cone snails use the venoms for rapid prey immobilization. The peptide components in the venoms target a wide variety of membrane-bound ion channels and receptors. A large number have been found to be highly selective for a diverse range of mammalian ion channels and receptors associated with pain signaling pathways.

Their small size, structural stability and target specificity make these attractive pharmacological agents, Krishnan told sources.

"As expected from the evolutionary history of these venom components, our search has yielded novel peptides of therapeutic promise from the new species that we have studied," Krishnan said.

"NCSB-TIFR has already collected and identified about 50 of estimated 80 of the genus conus (cone snail) from Indian coasts and more than 40 bioactive peptides were isolated from nine species," Krishnan said.

"The scientists have also sequenced seven peptides and isolated novel 13 residue acyclic peptides that target non-inactivating potassium channels, characterized from conus monile and this has been patented, "Krishnan said.

"Another peptide modulating sodium channel activity was isolated from conus amadis and its solution structure is determined and this is also patented in view of its potential for clinical use, "he said.

"We have already patented three different peptides and are ready for drug development and pharma companies will be undertaking various trials starting from toxicity, safety and efficacy before beginning any clinical trial," Krishnan said.

"We have also begun a comprehensive programme for the identification and characterization of peptides from cone snails found in Indian Coastal waters a couple of years back and the quick results show India could become a leader in this area of pain relievers once the research is done on a war footing," Krishnan pointed out.

Another peptide modulating sodium channel activity was isolated from Conus amadis and its solution structure is determined and this is also patented in view of its potential for clinical use, said Krishnan who has been working on the nervous system of fruit fly `Drosophila' for over two decades.

For any drug discovery, both modern and ancient, it is of great interest in analysis of plant and animal toxins as starting points. Ayurveda and other traditional medicine systems from around the world generally use plant-derived material as cures. Rare, however, are examples of animal venoms and toxins as prospective drugs.

The general observation is that animals use venoms for both prey capture and defence. In particular, a weak and slow moving animal is more or less likely to target the enemies' or prey species' nervous system because of need for rapid action.

"Marine cone snails represent one such class and are the largest single genus of venomous predators estimated at about 500 species and are widely distributed in Indo-Pacific," Krishnan said.

They prey on fish, marine worms and molluscs. Cone snails have evolved mechanisms to generate a library of toxic peptides, which act in concert to rapidly immobilize prey by simultaneously targeting several receptors and channels.