Australia is well-known as the home of venomous animals. From snakes and spiders to stonefish and scorpions, over millions of years our native fauna have evolved an array of chemical compounds to specifically target the nervous or cardiovascular systems of their predators and prey. These compounds are fast-acting, extremely potent, and incredibly selective in their action – exactly the qualities we want in pharmaceuticals.
Dr Evelyne Deplazes, Research Fellow in the School of Biomedical Sciences, is using molecular dynamics simulations and data from spectroscopy experiments to investigate how venom peptides bind to cell membranes, with a view towards peptide-based drug design. It’s not a new idea: venomous animals have a long history as a source of medical treatments. Snake venom was documented in the seventh century B.C. to treat arthritis, and cobra venom has been used since the 1930s to treat conditions including polio, multiple sclerosis and chronic pain.
“We’ve only been able to study spider venoms more recently”, explains Deplazes. “You get a lot less venom milking a spider than you do milking a snake! We’ve only recently had chromatographic techniques sensitive enough to separate out the venoms into their individual components and analytical techniques to characterise their structures routinely. Spider venoms are very complex mixtures and contain hundreds of distinct components, most of which are peptides that target the nervous system.”
As our understanding of the nervous system develops and the actions of the various ion channels in cell membranes become better understood, new therapeutic targets are emerging that spider venoms may be able to unlock. Specific ion channels have been identified for their involvement in pain sensation, so peptides that selectively inhibit these channels might be useful leads in the development of novel painkillers. Equally, as the neurological basis for blood pressure regulation, cardiac arrhythmia, epilepsy, multiple sclerosis and stroke become better understood, venom peptides that interact with these pathways will become a basis for new treatments.
“Most of these venom peptides involve interactions with receptors in cell membranes”, says Deplazes. “Understanding that interaction is the key to understanding how they work, and which bits of the peptide structure are important for that activity. We are combining computer simulations of the interaction with experimental data to get a more complete picture of how things work at the molecular level. Once we have that understanding, we can start tweaking the peptide properties to suit our purpose. The aim is to use rational design approaches to create a venom peptide analogue with all of the potency, selectivity and specificity of the original venom, but the activity we want to be therapeutically useful.”
Deplazes is currently working on venom peptides from the Peruvian green velvet tarantula as a lead for chronic pain treatment, and venom from the Trinidad tarantula with potential for stroke treatment. But she is keen to search further – who knows what therapeutic potential may be lurking in our funnelwebs, WA trapdoors and redback spiders?