Snakes have long been a powerful symbol in myths and legends. In ancient times, they represented regeneration and wisdom, but in modern times they are often remembered as objects of fear and disgust. Especially in myths and fairy tales, snakes are often depicted as symbols of death and suffering, evoking caution and dread in many people. In fact, statistics show that about 63,000 people lose their lives to snake venom each year, illustrating the deadly threat of snakes.
However, snake venom is not merely a symbol of fear. While it poses a lethal threat to humans, its complex chemical composition is gaining attention as a crucial key to advancements in modern science and medicine. Research on snake venom has become an important tool in understanding the body's complex physiological functions and developing new treatments.
◇From intravenous injections to oral therapies… advancements in snake venom treatments
Snake venom consists of complex chemicals that cause various symptoms such as nerve paralysis, tissue damage, and bleeding. The composition of venom varies by species, while the toxins primarily attack the nervous system, inhibit blood coagulation, and cause tissue destruction, among other lethal effects.
In the past, antivenom treatments were developed to prevent harm from snake venom. This involved injecting weakened snake venom into animals, extracting the antibodies produced, and administering them to patients to save lives.
However, antivenom treatments have several limitations. First, they are effective only against specific snake venoms, and antivenom can be difficult to obtain in rural areas where snakebites frequently occur. Additionally, intravenous injections are required, making immediate treatment in emergencies challenging, and there is a possibility of severe allergic reactions. To address these issues, researchers are currently seeking new treatment methods.
First, the method of recycling existing drugs is opening up new possibilities in snake venom treatment. A notable example is 'varespladib,' which was developed as a cardiovascular treatment. This drug is effective in reducing the toxicity of snake venom by inhibiting the 'sPLA2' enzyme, a principal toxin found in 95% of snake venoms. Notably, varespladib is an oral medication that can be easily used even in emergencies.
'Unityol,' a drug previously used for treating heavy metal poisoning, is also gaining attention as a snake venom treatment. Unityol helps expel heavy metal ions from the body and neutralizes the metal ions of metalloproteinase enzymes, which are key components of snake venom, thereby reducing its toxicity. Such drugs have the potential to penetrate tissues inaccessible to antivenom, overcoming limitations of existing treatments. Clinical trials on animals and humans are currently underway.
◇New antibodies and AI: innovative technologies for snake venom treatment
To overcome the disadvantages of traditional antivenom, new antibody-based therapies are also being researched. For instance, an antibody named '95Mat5' effectively inhibits cobra and mamba venoms while posing a lower risk of allergic reactions compared to existing antivenoms. In experiments with mice, after administering snake venom followed by the antibody 10–20 minutes later, the mice survived for over 24 hours. In contrast, the untreated mice died within three hours.
NANO antibodies extracted from llamas and alpacas are also drawing attention. NANO antibodies, due to their small size, can bind to specific components of snake venom more quickly and accurately, while being less expensive and more stable. To produce these antibodies, researchers inject 18 types of mamba and cobra venoms into llamas and alpacas and extract the DNA of the white blood cells generating the antibodies. Following this, research is ongoing to analyze the DNA to select the most effective NANO antibodies for snake venom.
This year’s Nobel Prize in Chemistry winner, Professor David Baker of the University of Washington, and his team have also designed new proteins that can bind to snake venom using artificial intelligence (AI). The proteins designed by the team were injected into mice, showing significant protective effects against the toxins.
◇Pharmaceuticals inspired by snake venom
Snake venom also plays an important role in drug development. It consists of bioactive substances such as enzymes, proteins, and peptides that are designed to act lethally on various body systems. Thanks to its ability to rapidly and precisely target substances, it also inspires researchers in drug development.
A prime example is the antihypertensive drug captopril. In the 1980s, a specific peptide discovered in the venom of the Brazilian pit viper was effective in inhibiting the action of enzymes that regulate blood pressure. This peptide inhibited the excessive action of the 'angiotensin-converting enzyme (ACE),' which constricts blood vessels to regulate blood pressure. When this enzyme is blocked, blood vessels relax and blood pressure drops.
Researchers designed captopril to mimic the actions of natural peptides found in snake venom while ensuring it is safer and more effective for humans. Captopril, developed based on this, is currently used for treating heart failure and hypertension, saving millions of lives worldwide.
Regarding this, Mende Holford, a professor at Hunter College and the City University of New York, noted, "Venom is like a cluster bomb that simultaneously acts on various systems, which makes it a useful tool for exploring multiple possibilities in new drug development."
References
Nature (2024), DOI: https://doi.org/10.1038/d41586-024-03818-z