Synthetic antibody developed to neutralise deadly snakebite toxin

New Delhi: Scientists have developed a synthetic human antibody that can neutralise a deadly toxin produced by a variety of snakes. The study, published in the journal Science Translational Medicine, adapted an approach used earlier to screen for antibodies against HIV and COVID-19 to synthesise the new venom-neutralizing antibody. This is the first time that this particular strategy is being applied to develop antibodies for snakebite treatment," said Senji Laxme, a PhD student at the Indian Institute of Science (IISc), Bengaluru. The team, including researchers from US-based Scripps Research Institute, noted that the study is a step towards a universal antibody solution that can offer broad protection against the venom of a variety of snakes, which includes the cobra, king cobra, krait and black mamba.

Snakebites cause thousands of deaths every year, especially in India and sub-Saharan Africa, they said. The current strategy for developing antivenoms involves injecting snake venom into equines like horses, ponies and mules, and collecting antibodies from their blood. However, there are several problems with that approach. "These animals get exposed to various bacteria and viruses during their lifetime," said Kartik Sunagar, Associate Professor at IISc and joint corresponding author of the study.

"As a result, antivenoms also include antibodies against microorganisms, which are therapeutically redundant. Research has shown that less than 10 percent of a vial of antivenom contains antibodies that are targeted towards snake venom toxins," Sunagar said. The antibody developed by the team targets a conserved region found in the core of a major toxin called the three-finger toxin (3FTx) in the elapid venom. Although different species of elapids produce different 3FTxs, a handful of regions in the protein are similar, the researchers said. The team zeroed in on one such conserved region a disulphide core. They designed a large library of artificial antibodies from humans, which were displayed on yeast cell surfaces. They then tested the antibodies' ability to bind to 3FTxs from various elapid snakes around the world.

After repeated screening, the researchers narrowed down their choices to one antibody that could bind strongly to various 3FTxs. Among the 149 variants of 3FTxs in public repositories, this antibody could bind to 99, they said. The researchers then tested their antibody in animal models. In one set of experiments, they pre-mixed the synthetic antibody with a toxic 3FTx produced by the Taiwanese banded krait and injected it into mice.

Mice given just the toxin died within four hours. But those given the toxin-antibody mix survived past the 24-hour observation window and looked completely healthy, they said. The team also tested their antibody against the whole venom of the monocled cobra from Eastern India and the black mamba from sub-Saharan Africa and found similar results. The efficacy of the antibody was found to be nearly 15 times that of the conventional product, the researchers added.