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Insight into snake venom evolution could aid drug discovery

Natural Environment Research Council press release

UK-led scientists have made a discovery about snake venom that could lead to the development of new drugs to treat a range of life-threatening conditions like cancer, diabetes and high blood pressure.

Most venom contains a huge variety of lethal molecules called toxins, which have evolved from harmless compounds that used to do different jobs elsewhere in the body. These toxins target normal biological processes in snakes’ prey such as blood clotting or nerve cell signalling, stopping them from working properly.

Now researchers have discovered that the toxins that make snake and lizard venom deadly can evolve back into completely harmless molecules, raising the possibility that they could be developed into drugs.

NERC-funded researcher and lead author of the study, Dr Nicholas Casewell from Liverpool School of Tropical Medicine, explains:

‘Our results demonstrate that the evolution of venoms is a really complex process. The venom gland of snakes appears to be a melting pot for evolving new functions for molecules, some of which are retained in venom for killing prey, while others go on to serve new functions in other tissues in the body.’

Scientists have long recognised that the way that toxins work makes them useful targets for drug discovery. But the fact that they’re harmful poses a problem. This means that drug developers have had to modify toxins to retain their potency and make them safe for drug use.

But the researchers’ discovery that there may be many harmless versions of these toxins throughout a snake’s body opens the door to a whole new era of drug discovery.

Snake researchers were aware that venom toxins evolve from harmless molecules that do fairly mundane jobs elsewhere in the body. But until now they had assumed that this was a one-way process.

Casewell and colleagues from Bangor University and the Australian National University used recently published gene sequences from the Garter snake and the Burmese python in their study. They compared these sequences with those from venom glands in a wide range of snakes and lizards, constructing an evolutionary tree to work out the relationships between the various sequences.

Dr Wolfgang Wüster from Bangor University, a co-author of the study says:

‘Many snake venom toxins target the same physiological pathways that doctors would like to target to treat a variety of medical conditions. Understanding how toxins can be tamed into harmless physiological proteins may aid development of cures from venom.’

The researchers’ findings are published in Nature Communications today.

Publication date: 19 September 2012