Deadly Snake Venom Is No Match for This New Synthetic Antibody

Researchers have created a powerful synthetic antibody that counteracts the deadly venom produced by snakes in the Elapidae family—which includes the black mamba, king cobra and kraits. Their findings, published last week in Science Translational Medicine, offer hope for an eventual universal antivenom, one capable of neutralizing the toxins of hundreds of venomous snakes worldwide.

“We are wiping out a major subclass of neurotoxins here,” says Nicholas Casewell, a co-author of the study and a toxinologist at the Liverpool School of Tropical Medicine in England, to Science’s Christie Wilcox. “I think this is a really huge step in terms of what can be achieved by a single antibody.”

Venomous snake bites claim the lives of an estimated 81,000 to 138,000 people annually and leave more than 400,000 people with permanent disabilities. With a complex cocktail of damaging proteins, snake venom acts as a “chemical weapon,” attacking the nervous system, tissues or blood stream. Compared to their devastating impact, the level of research on venomous snake bites is low, and the World Health Organization listed these bites as a highest priority neglected tropical disease in 2017.

Antivenoms exist, but they are “built with 100-year-old technology,” says Joseph Jardine, a protein engineering expert at Scripps Research, to Science News’ Meghan Rosen. To develop most antivenoms, scientists inject horses or other animals with doses of the snake venom and harvest the antibodies their immune systems produce as a result—a process that is both dangerous and limiting. For one, the specific antibodies aren’t guaranteed to work on the victim. Snake venoms differ across species, and treatment must be precise—though it’s not always known which species has bitten a person. And, even if administered accurately, the animal proteins in the drugs have the potential to cause fatal anaphylaxis.

“These animals get exposed to various bacteria and viruses during their lifetime,” says Kartik Sunagar, head of the evolutionary venomics lab at the Indian Institute of Science and a lead author of the paper, in a statement. “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 actually contains antibodies that are targeted toward snake venom toxins.”

Sunagar’s team sought to sidestep these risks by targeting the core component of a major toxin in Elapidae snakes’ venom: long-chain three-finger alpha-neurotoxins. The molecules in this neurotoxin “look like a small hand with three fingers,” per Science News, and they cause paralysis by shutting down a protein critical for movement, Andreas H. Laustsen-Kiel, a toxicologist at the Technical University of Denmark who was not involved in the study, tells the publication.

Using a screening method previously used on antibodies for fighting HIV and Covid-19, researchers pored through at least 60 billion artificial human antibodies to pinpoint which grasped onto the three-finger alpha-neurotoxin the tightest. The antibodies that are best able to hold on can most effectively neutralize its toxicity. Researchers identified about a dozen of their top candidates, but in tests on human cells, one stood out.

The teams then tested this antibody on animal models. Groups of five mice were given a life-threatening dose of the toxin from the venom of a krait, mixed with the antibody. Mice that weren’t given the antibody died within four hours, but all of the treated mice survived.

Even when the antibody was delayed for 20 minutes after envenomation, the mice lived. So was the case for the venoms of monocled cobras and black mambas. The antibody, however, did not save mice from king cobra venom.

“If you had asked me six years ago, I would have said that you’d be out of your mind to think that you can neutralize a snake venom by targeting just one toxin,” says Sunagar to Science.

The antibody’s efficacy on the potent venom from a black mamba “really speaks to the fact that it is a good antibody,” Laustsen-Kiel adds to the publication.

Because the antibody is produced in a lab from cell lines derived from humans, it avoids harmful side-effects connected to animal antibodies.

“This solves two problems at the same time,” says Sunagar in the statement. “First, it is an entirely human antibody and hence, side-effects, including fatal anaphylaxis, occasionally observed in patients 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.”

Next, the researchers hope to extend their antibody-production strategy to other venom toxins. Their team believes that these antibodies can eventually be combined to create a concoction that shuts down the toxins of every venomous snake looming globally.

“You’d no longer have to stock hundreds of antivenoms,” Jardine says to Science. “You could stock a single universal one.”

Catherine Duncan | READ MORE

Catherine Duncan is an intern with Smithsonian magazine.