One of the challenges in treating snakebite, especially in India which has as many as 62 species of venomous snakes, lies in first identifying what kind of snake has bitten a person, which is crucial to identifying the right antivenom that would need to be administered. Since the species is often difficult to identify, could the answer lie in developing a universal antivenom, a one-shot solution that could neutralise the venom from a variety of snake species?
Scientists from the Scripps Research Institute in California and the Indian Institute of Science (IISc) Bangalore have taken a step in that direction. They have developed an antibody that can block the effects of toxins in the venoms from a wide variety of snakes, and published their findings from trials in mice in Science Translational Medicine last week.
It is important to underline here that this breakthrough is still a long way from a universal antivenom. The antibody works against a family of toxins that is secreted by a large group of snakes, but not all snakes. Specifically, the toxins it neutralises are present in the venom of “elapids”, or members of the Elapidae family that includes cobras, the king cobra and kraits (all of which populate India) besides mambas. The antibody does not target the venom from vipers, which claim many lives in India. Besides, even cobra venom contains additional lethal toxins beyond those that the antibody targets.
Nevertheless, a leading expert on snake venom, who was not involved in the study, acknowledged its significance. Professor Ashis K Mukherjee, a microbiologist with Tezpur University and currently on deputation to the Institute of Advanced Study in Science and Technology in Guwahati as its director, is an expert member on WHO’s Strategic Plan for Control and Prevention of Snakebite.
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“Yes, this synthetic antibody against a particular neurotoxin may not show any benefit against envenomation by the Viperidae family of snakes such as Russell’s viper and saw-scale viper,” Mukherjee said. “Despite this limitation, I can see that this study has a great future that can pave the way for developing several other toxin-neutralising antibodies. A cocktail of such antibodies may protect better against snakebite than commercial antivenom,” he said. He called for clinical trials to validate the new findings.
Snakebite accounts for 58,000 deaths in India annually, according to estimates cited by the study’s corresponding author, Kartik Sunagar, an evolutionary geneticist whose lab at IISc investigates venomous animals and their venom. No countrywide figures from a government source are available, because snakebite is not a notifiable disease in India. In fact, it is notifiable in only one state, Karnataka, which made that decision only last week.
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How the antibody works
Researchers first identified which molecular region of venom toxins to target. Separately, they created a large library of artificial human antibodies and tested how they responded to these toxins. Their observations narrowed the hunt down to a single antibody, which they tested on mice, with encouraging results.
Among the deadliest toxins present in the venom of elapid snakes are a group called three-finger toxins (3FTx), which disrupt neurotransmission in the victim and cause paralysis. These are proteins whose structure differs between one elapid snake species and another, but some regions are similar across species. The researchers targeted one of these conserved regions.
With a library of artificial antibodies on one hand, and 149 variants of 3FTx from various elapid snakes on the other, the reporters examined their interactions. One antibody was found to bind strongly to 99 of the 149 3FTx variants.
Researchers mixed this antibody separately with venom taken from the Indian monocled cobra, the Taiwanese banded krait, and the African black mamba. Mice injected with the mix survived and looked healthy. When they injected the venom first and the antibody after a delay (0, 10 or 20 minutes), the mice again survived.
The researchers also tested a conventional product on mice, and found that it worked well only when it was injected alongside the venom; a delay of even 10 minutes reduced its efficacy. The new antibody was found to have an efficacy 15 times higher than that of the conventional antivenom.
Why it matters
Sunagar of IISc dwelt on the challenges associated with treating snakebite in India. “Antivenoms are made by collecting venom from just one or two districts in Tamil Nadu. And this is used for treating snakebite all across India and neighboring countries,” he said. “We have shown that these antivenoms don’t work very effectively in several pockets of India including, for example, in the northern parts of India. Even here in Karnataka, the antivenoms are not very effective because we either find very different snakes here or the same species of snakes produce very different toxins.”
If the snake species could be identified after a bite, the treatment could have been specific to that species. However, if the snake has gone away, there is no diagnostic kit that could detect the snake venom in the patient’s body fluid, Mukherjee of IASST said. “Due to the lack of venom detection kits, administering polyvalent antivenom against the venoms of the ‘Big Four’ snakes (spectacled cobra, common krait, Russell’s viper and saw-scaled viper) is India’s only treatment choice. However, this therapy is associated with several adverse reactions,” he said.
Studies by Mukherjee and colleagues have found toxins of the 3FTx group account for 30-75% of cobra venom. The conventional source of antibodies is by generating them in horses, but not enough antibodies against 3FTx are produced this way. “Therefore, commercial polyvalent antivenoms contain a lower proportion of neutralising antibodies against [such toxins]. As a result, commercial antivenom is ineffective in neutralising these toxins, a hurdle for effective therapy against snakebites.”
As such, the first significance of the new antibody is that it can neutralise the toxicity of this clinically important neurotoxin, he said.
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The road ahead
While Mukherjee stressed the need for clinical trials, Sunagar believes the antibody is not yet ready for these; given its limitations, it is not yet something clinicians can rely on.
Sunagar’s lab at IISc and that of immunologist and microbiologist Joseph Jardine at Scripps are looking to identify antibodies against other toxins.
So, what is the future? Like Mukherjee, Sunagar too suggests a potential cocktail of antibodies. A universal antivenom would consist of a couple of synthetic antibodies that “would hopefully neutralise venoms of most snakes in various parts of the world”.
Rohit Malhotra is a medical expert and health journalist who offers evidence-based advice on fitness, nutrition, and mental well-being. His articles aim to help readers lead healthier lives.
