A team of scientists based at Bangor University have made a discovery that has kick-started explorations into creating new therapeutics from snake venom. If successful, drugs that treat serious diseases and illnesses including cancer, diabetes, and cardiovascular problems could be treated with this new type of drug.
Image Credit: Maria Dryfhout/Shutterstock.com
The evolution of snake venom
The toxins that makeup snake venom evolve from harmless compounds that have other purposes in the snake’s body. These compounds start life carrying out often very mundane tasks but then develop into a lethal molecule with capabilities to disrupt the biological processes of the snake’s prey, such as blood clotting or nerve cell signaling.
The reason harmless proteins within the snake evolve into toxins is because of the continual evolution of the snake’s prey, which adapts to the venom, building resistance, eventually rendering the venom ineffective. As a result, the toxins found in snake venoms are the fastest-evolving proteins that have never been identified.
Scientists had long assumed that this process that converts harmless compounds into toxins was one way. This was until researchers discovered that these toxins can convert back into harmless molecules. The venom gland of a snake contains a multitude of molecules, many of which are evolving new functions, some molecules will evolve to serve as prey-killing venom, and others will transform back into harmless molecules that carry out mundane tasks in the body. This discovery highlighted the potential role that snake venom has to play in developing new drugs.
Converting venom into harmless substances to develop revolutionary drugs
The toxins many functions make them incredibly useful targets for the development of novel therapeutics. However, their toxicity renders them useless therapeutically, until they can be adapted into harmless substances. Drug developers spend a lot of time and resources modifying toxins so that they can retain their potency without their toxicity. It is an incredibly challenging task.
One drug that has been developed in this way is a drug that treats high blood pressure, known as Captopril, was created by modifying the chemical structure of a compound found in the venom of the lancehead viper. The compound’s usual role within the venom is to lower the blood pressure of its prey, low enough to kill it. Scientists saw the opportunity to develop this compound to develop a safe drug for lowering blood pressure.
With the discovery that venom toxins may exist in harmless versions within the snake’s body, an entirely new realm of drugs has been made possible. Scientists may be able to locate harmless compounds that have beneficial functions that can be leveraged into drug development.
Compounds that used to function as toxins are of interest to drug development scientists as they contain bioactive proteins that target metabolic processes. Therapeutics are designed to target metabolic processes, so the fact that ex-venom proteins already do this is very valuable.
Harmless ex-venom proteins offer scientists the opportunity to look to nature to find compounds that have the functions they need without developing synthetic drugs. Molecules from the snake could be screened to check for targeted functionalities.
In a study which brought together scientists Bangor University, Wales, and the Australian National University, gene sequences from the Garter snake and the Burmese python were compared against species of snake with venom, as well as against a range of venomous lizards, which enabled them to develop an evolutionary tree establishing the relationships between the numerous gene sequences.
The evidence gathered confirmed that some proteins evolve back into harmless molecules and go on to carry roles in other areas of the body. Before this, it had been assumed that proteins had evolved from carrying out normal bodily processes to become toxic components of venom, it had not been considered that the transformation could occur backward as well.
Because snake venom toxins often target the exact physiological pathways that scientists wish to target with new therapeutics, this discovery is an incredibly important step forward for the field of drug discovery. More research is required to gain a deeper understanding of how toxins transform into harmless proteins, which will undoubtedly help scientists progress their work in creating new drugs from venom.
Given that there are around 600 species of venomous snakes in the world, this discovery opens up an entire branch of drug discovery, the fruits of which are yet to ripen. We are in the very early stages of this drug development area, which may produce numerous effective drugs to treat a wide range of illnesses over the coming years.
Additionally, this research indicates that studies involving other venomous animals may also be worthwhile for drug discovery purposes. Scientists now have far more places to look to gain inspiration for new therapeutics.
- Bordon, K., Cologna, C., Fornari-Baldo, E., Pinheiro-Júnior, E., Cerni, F., Amorim, F., Anjolette, F., Cordeiro, F., Wiezel, G., Cardoso, I., Ferreira, I., Oliveira, I., Boldrini-França, J., Pucca, M., Baldo, M. and Arantes, E., 2020. From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery. Frontiers in Pharmacology, 11. https://www.frontiersin.org/articles/10.3389/fphar.2020.01132/full
- Casewell, N., Huttley, G. and Wüster, W., 2012. Dynamic evolution of venom proteins in squamate reptiles. Nature Communications, 3(1). https://www.nature.com/articles/ncomms2065
- Mohamed Abd El-Aziz, Garcia Soares and Stockand, 2019. Snake Venoms in Drug Discovery: Valuable Therapeutic Tools for Life Saving. Toxins, 11(10), p.564. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832721/