Scientists develop synthetic antibody for deadly snake venom toxin

Scientists from the Scripps Research Institute and the Evolutionary Venomics Lab (EVL) at the Centre for Ecological Sciences (CES), Indian Institute of Science (IISc) have engineered a synthetic human antibody capable of neutralizing a potent neurotoxin found in snakes of the Elapidae family.

These snakes, including the cobra, king cobra, krait, and black mamba, are notorious for their lethal venom.

The team employed a novel approach, previously utilized in screening antibodies against HIV and COVID-19, to create this venom-neutralizing antibody, marking the first time such a strategy has been applied to combat snakebite toxins.

PhD student at EVL, CES, and co-first author of the study published in Science Translational Medicine, Senji Laxme RR, emphasized the significance of this achievement.

“This is the first time that this particular strategy is being applied to develop antibodies for snakebite treatment,” Laxme said.

Snakebites cause thousands of deaths every year, especially in India and sub-Saharan Africa. The traditional method of producing antivenoms involves injecting snake venom into equines like horses, ponies, and mules, and then harvesting antibodies from their blood. However, this approach presents numerous challenges.

Associate Professor at CES and joint corresponding author of the study, Kartik Sunagar, explained that current antivenoms contain redundant antibodies against various microorganisms due to the animals’ exposure during their lifetimes. Consequently, less than 10% of the antivenom typically consists of antibodies targeting snake venom toxins.

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The newly developed antibody targets a conserved region within the core of a major snake venom toxin known as the three-finger toxin (3FTx). By focusing on this region, the team designed a diverse library of artificial antibodies from humans, displayed on yeast cell surfaces. After rigorous screening, they identified one antibody capable of binding strongly to various 3FTxs from different elapid snakes worldwide.

Animal trials demonstrated the antibody’s effectiveness in neutralizing venom from snakes like the Taiwanese banded krait, monocled cobra, and black mamba, surpassing the potency of conventional antivenom by nearly 15 times. The synthetic antibody retained its efficacy even when administered after a delay following venom injection, unlike traditional antivenom.

Further analysis using cryo-electron microscopy revealed the intricate binding between the toxin and the synthetic antibody, mimicking the interaction between the toxin and receptors in nerve cells and muscles. The discovery suggests a potential mechanism for the antibody’s ability to displace toxins bound to receptors.

Moreover, the antibody’s production using human-derived cell lines eliminates the need for animal testing, addressing ethical concerns and reducing the risk of allergic reactions in patients.

“Because the antibody is fully human, we don’t expect any off-target or allergic responses,” Laxme adds.

“This solves two problems at the same time,” says Sunagar. “First, it is an entirely human antibody and, hence, side-effects, including fatal anaphylaxis, occasionally observed in patients being treated with conventional antivenom, can be prevented. Secondly, this would mean that animals need not be harmed in future to produce this life-saving antidote.”

Sunagar highlighted the broader implications of this research, envisioning a future where multiple synthetic antibodies could form a universal antivenom therapy, effective against a wide range of snake venoms worldwide. The team is optimistic about advancing to human clinical trials, aiming to revolutionise snakebite treatment and save countless lives globally.