Snake venom: natural pharmacopoeia
Snake venom toxin researcher R. Manjunatha Kini, a professor at National University of Singapore and founder of a couple of companies working on venom therapeutics, spoke to Nature India on his love for all things toxic.
doi:10.1038/nindia.2010.176 Published online 15 December 2010
Q. What does research in snake venom toxins entail?
A. Snake venom is another source of pharmacologically active peptides. Snake venom toxins evolved over millions of years to target prey animals including mammals. Since humans are mammals, the toxins target specific ion channels and receptors in the human body too.
Snake venom is obviously not made to kill humans but rats and mice. If we can identify these new toxins, which are very unique in their properties to target specific receptors, the information would be very useful in designing drugs for human diseases. For example, there are a lot of toxins which block blood clotting and platelet aggregation.
Q. What are the potential applications of snake venom toxins research?
A. Snake venoms are natural pharmacopoeia with more than 100 proteins and polypeptides that have distinct pharmacological properties. In the past, only the most toxic and the most abundant proteins were studied. With the advent of new technologies, we are now able to study proteins that are found in small amounts. We can also study venoms of snakes that yield low quantities of venom. A number of these new toxins provide interesting new tools as well as new leads for therapeutic prototypes. Thus there are many potential applications.
Q. What does your research focus on?
A. I have worked on phospholipase A2 (PLA2) enzymes obtained from snake venom for over 25 years. We have also worked on a number of other families of snake venom toxins such as three-finger toxins and serine proteinases (prothrombin activators). We have characterized more than a dozen new three-finger toxins. Some of them have unique targets. For example, we identified the first natural beta-blocker named beta-cardiotoxin. We identified a number of unique neurotoxins and anticoagulant proteins. Our lab has identified several new families of snake venom toxins, namely waprins, vesprins and veficolins.
Q. Do you also synthetically design any therapeutic peptides?
A. Yes. We design and develop short bioactive peptides based on the functional sites of toxins. So far we have developed an analgesic peptide, a couple of anticoagulant and antiplatelet peptides and a hypotensive peptide based on toxin structure. The analgesic peptide is under preclinical toxicology studies. If everything goes well it should enter human clinical trials in the next year or two.
Q. What drew you to snake venom toxins research?
A. I was born and brought up in the Malnad area of India's Western Ghats (Shimoga, now Shivamogga). I have seen quite a number of deadly snakes as a kid and was always fascinated by them. There were many anecdotal evidences around on treatment of snake bites with Indian medicinal plants. I started my research work on isolating plant components that neutralize snake venom toxicity under the guidance of Prof. T. Veerabasappa Gowda.
During this time, Prof. Gowda and I learnt a lot about snake venom toxins. We recognized that snake venom proteins were similar to our own body proteins. So my postdoctoral research tried to understand why snake venom toxins are toxic while our body proteins are not. These studies led me to think about why we cannot use them as therapeutic leads. Since then, I have been working of the theme "from toxins to therapeutics".
Q. Besides the therapeutic potential, can snake venom toxins shed light on their evolution and place in the ecological niche?
A. Yes. Indeed toxins can shed light on evolution. Some of the new phenomena we and others have discovered indicate accelerated evolution of snake venom toxins.
Q. Could their therapeutic potential be used to campaign for preservation of snake species?
A. As we understand more and more toxins from unique snake species, we discover newer and unique toxins. This provides us with a number of new drug prototypes as well as research tools. Thus it gives us ample reason to urge for preservation of various snake species.