For many individuals, snakes evoke a sense of fear and danger, particularly in regions of India and Africa where snakebites pose a significant threat to human life. Each year, venom from snakebites claims over 100,000 lives and leaves approximately 400,000 individuals with permanent disabilities. This burden is particularly high in low and middle-income countries in Africa and Asia, with India alone accounting for a staggering 58,000 fatalities annually, according to a 2020 report. Despite the devastating impact of snakebites, relatively little attention has been paid to this issue, often referred to as a “poor man’s disease.”
In 2017, the World Health Organization (WHO) recognized the urgent need to address this hidden health crisis and classified snakebite envenoming as a neglected tropical disease. However, the current process of producing antivenom, which involves extracting antibodies from the blood of large animals injected with snake venom, has limitations. The antibodies derived from animals may contain impurities and can trigger adverse reactions in humans. Animal-derived antivenoms also have limited effectiveness against the diverse range of snake species and venom compositions.
Recognizing these challenges, a team of scientists sought an alternative approach. Funded by the Wellcome Trust, they developed a synthetic human antibody that targets a specific type of toxin commonly found in snake venoms. Their findings were recently published in the journal Science Translational Medicine.
“Venoms of snakes in India are so diverse that venoms of the same species across regions can’t be neutralised by the same antivenom,” said Kartik Sunagar, head of the Evolutionary Venomics lab at the Indian Institute of Science, Bengaluru, and one of the lead authors of the study. “Even in the same geographical location, if you look at individuals of the same species, antivenom can only neutralise some venoms and not others. There is a stark variation in venoms, so that’s why we wanted to figure out a solution that might work across regions and across species.”
The scientists focused on three-finger toxins (3FTxs), a potent and abundant component of elapid snake venoms. Elapids include medically significant snakes such as cobras, kraits, and mambas. They specifically targeted α-neurotoxins, a class of 3FTxs that disrupt nerve and muscle function by blocking the binding of acetylcholine, a neurotransmitter essential for muscle movement. This leads to paralysis, respiratory failure, and potentially death.
The scientists screened billions of human antibodies to identify those that could effectively bind to the toxins. After multiple rounds of screening, they selected an antibody named 95Mat5 that exhibited broad reactivity against various 3FTx variants.
Subsequent testing in human cells and mice confirmed the neutralizing capabilities of 95Mat5 against venoms from multiple elapid snakes. The antibody protected mice from lethal doses of venom from black mambas, monocled cobras, and many-banded kraits. However, it had limited efficacy against the venom of king cobras, suggesting the need for further research to address the full range of venom diversity.
Andreas Hougaard Laustsen-Kiel, head of the Tropical Pharmacology Lab at the Technical University of Denmark, who was involved in a similar study published last year, commented, “The study is really well-performed, and I would expect that the antibody could be used as an important component in future antivenoms against mambas and cobras in Africa and Asia.”
Dr. Sunagar emphasized the importance of their findings: “Because snake venoms are so complex, I would have thought it impossible to make an antibody that could knockout the whole venom.” He and his colleagues believe that the development of specific antibodies against toxins in other snake venoms could lead to a universal antivenom solution.
Rohini Subrahmanyam, a freelance journalist, contributed to this article.
