An Indian spectacled cobra, a member of the Elapidae family of snakes, on the IISc campus
Credit: Kartik Sunagar
Bengaluru: Scientists at the Indian Institute of Science (IISc) here have developed a synthetic human antibody that can neutralise a potent neurotoxin produced by highly toxic snakes of the Elapidae family, which includes the cobra, king cobra, krait, and black mamba.
A team of researchers at the Scripps Research Institute and the Evolutionary Venomics Lab (EVL) at the Centre for Ecological Sciences (CES) adapted an approach used earlier to screen for antibodies against HIV and COVID-19 to synthesise the new antibody.
Senji Laxme R R, PhD student at EVL, CES, and co-first author of the study published in Science Translational Medicine, said the strategy was used for the first time to develop antibodies for snakebite treatment.
Thousands of snakebite deaths are reported every year, especially in India and sub-Saharan Africa. The current antivenom strategy – injecting snake venom into equines like horses, ponies, and mules, and collecting antibodies from their blood – comes with problems.
Kartik Sunagar, Associate Professor at CES and joint corresponding author of the study, noted that these animals are exposed to various bacteria and viruses, which means that the resultant antivenoms also include antibodies against microorganisms which are therapeutically redundant. “Research has shown that less than 10% of a vial of antivenom contains antibodies that are targeted towards snake venom toxins,” he said.
The newly developed antibody targets a conserved region in the core of a major toxin called the three-finger toxin (3FTx) in the elapid venom, IISc said.
The researchers tested the ability of artificial antibodies, designed from humans, to bind to 3FTxs from various elapid snakes. They conducted extensive screening before zeroing in on an antibody that could bind strongly to various 3FTxs. Among the 149 variants of 3FTxs in public repositories, it could bind to 99, IISc said.
A safer antidote
In a subsequent experiment on animal models, the researchers pre-mixed the antibody with a toxic 3FTx produced by the Taiwanese banded krait and injected it into mice. While mice given just the toxin died within four hours, those given the toxin-antibody mix survived past the 24-hour observation and looked healthy.
Similar results were achieved against the venom of the monocled cobra from eastern India and the black mamba from sub-Saharan Africa. IISc said the antibody’s efficacy was nearly 15 times that of the conventional product.
“Crucially, when they first injected the venom and then gave the antibody after a time delay – 0 minutes, 10 minutes, and 20 minutes – the antibody was still able to save mice. The conventional product, however, only worked well when injected alongside the venom,” it said.
Since human-derived cell lines were used for the antibody, animals need not be harmed with injections. Secondly, the use of an entirely human antibody rules out side effects from conventional antivenom.
The researchers are working toward antibodies against other snake venom toxin targets.
“A universal antivenom in the future would consist of a couple of such synthetic antibodies that would hopefully neutralise venoms of most snakes in various parts of the world. A universal product, or at least a cocktail of antibodies that work pan-India, could then be taken to human clinical trials,” Sunagar said.