Author: Becky Li
Editors: Viola Chen and Sophia Chen
Artist: Sally Sun
Over time, snakes have acquired an infamous reputation. Known for their deadly venom and ability to suffocate their prey to death, it is no wonder that these reptiles are apprehended. However, snakes not only have the power to kill, but they can also heal. In fact, snake venom can be utilized as medicine to combat cardiovascular diseases and provide effective therapeutics.
A healthy cardiovascular system is critical for survival because it delivers oxygen and nutrients to tissues while removing carbon dioxide and waste. Additionally, it performs repairs and defense mechanisms when necessary. However, cardiovascular diseases (CVD) such as hypertension (high blood pressure) and thrombosis (blood clots) impede the functions of this valuable system. Those with CVD may experience physical and emotional symptoms, such as sleeping difficulties, fatigue, depression, and chest pain, leading to an overall poorer quality of life.
Snakes wield their venom to quickly paralyze and predigest prey, making it far more potent than physical force. Their venom mostly contains enzymes and non-enzymatic peptides, among other toxic components (lipids, carbohydrates, metal ions, etc.). These toxins primarily affect cardiovascular and neuromuscular systems, inducing biological effects on a local and systemic level. Such effects include swelling, tissue necrosis (death), coagulopathy (the inability of blood to clot), and circulatory shock. Initially, scientists researched these life-threatening manifestations to understand individual molecules' characteristics and mechanisms of action. However, scientists soon realized that snake venom could be used for physiological processes and can even become a life-saving therapeutics for CVDs.
Discovered over half a century ago, snake venom can lower blood pressure in human victims. The toxin with this hypotensive effect is bradykinin-potentiating peptides (BPPs), naturally occurring peptides in our bodies that can cause blood vessels to dilate and increase permeability, leading to decreased blood pressure. Though, angiotensin-converting enzymes (ACE) rapidly break BPPs down, resulting in fleeting low blood pressure. This enzyme also processes another natural peptide, turning angiotensin I into angiotensin II, aiding vessel constriction. Due to its multiple ways to increase blood pressure and cause hypertension, ACE became a drug of inhibition. However, because of a lack of structural information on ACE, scientists struggled to create a powerful and orally available ACE inhibitor, until they discovered that the South American pit viper, Bothrops jararaca, has BPPs in its venom. BPPs inhibit ACE, thus lengthening and strengthening the effect of bradykinin. With this new information, the first ACE inhibitor, captopril, was designed based on studies of natural and synthetically modified variants of ACE inhibitors. Since then, ACE inhibitors have become one of the most essential classes of therapeutic agents to treat hypertension.
Similarly, some Brazilian scientists have discovered peptide Bc-7a and protein Lm-10a, which appear in snake B. cotiara’s venom. These peptides are functionally similar to captopril, an ACE inhibitor. While research is ongoing, there is an optimistic future for a new generation of antihypertensive agents.
Snake venom is also useful for inducing or preventing clots. Following an injury, blood clotting or coagulation occurs after a series of reactions activate blood coagulation factors. Immediately, insoluble clots seal the injury site to prevent further bleeding. Snake venom toxins can act as a procoagulant (promoting coagulation) or anticoagulant (inhibiting coagulation). The former are typically enzymes used as a reagent to diagnose hematological diseases (affecting the blood or blood-producing organs) or diagnostic agents to monitor anticoagulant treatments in patients. Anticoagulants can be enzymatic or non-enzymatic, which disrupt the blood coagulation process by depleting or binding and inhibiting clotting factors.
With numerous possibilities, snake venom is a hopeful source of novel drugs and compounds for treating CVDs. As technology advances, the understanding of toxins rapidly increases, and the future of manipulating toxins into therapeutics remains more promising than ever.
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