New gel could spell end of using horses in production of snake anti-venoms

Chemistry professor Ken Shea, right, and doctoral student Jeffrey O’Brien have developed a broad-spectrum snake venom antidote. Photo: Steve Zylius / University of California, Irvine
Chemistry professor Ken Shea, right, and doctoral student Jeffrey O’Brien have developed a broad-spectrum snake venom antidote. Photo: Steve Zylius / University of California, Irvine

A molecular gel developed by American researchers neutralizes deadly snake venom more cheaply and effectively than traditional anti-venoms that use horses to create antibodies against the poison.

Worldwide, an estimated 4.5 million people are bitten annually. Around 2.7 million people suffer crippling injuries and more than 100,000 die, most of them farm-workers and children in poor, rural parts of India and sub-Saharan Africa with little healthcare.

The existing antidote is made by injecting horses with venom, waiting weeks for the animals to develop antibodies, then extracting and processing their blood and shipping it to places that can afford it. The process is not allowed in the United States. Major suppliers have discontinued shipments to many markets.

The existing treatment requires slow intravenous infusion at a hospital and is costly. And the antidote only halts the damage inflicted by a small number of species.

Now, work by researchers at the University of California, Irvine, could ultimately revolutionize treatment, providing a much cheaper alternative.

“Current anti-venom is very specific to certain snake types,” explains doctoral student Jeffrey O’Brien, lead author of a recent paper published in the Journal of the American Chemical Society.

“Ours seems to show broad-spectrum ability to stop cell destruction across species on many continents, and that is quite a big deal.”

The researchers zeroed in on protein families common to many snakes, demonstrating that they could halt the worst effects of cobras and kraits in Asia and Africa, as well as pit vipers in North America.

The team synthesized a polymer nanogel material that binds to several key protein toxins, keeping them from bursting cell membranes and causing widespread destruction.

O’Brien knew he was onto something when the human serum in his test tubes stayed clear, rather than turning scarlet from venom’s typical deadly rupture of red blood cells.

Chemistry professor Ken Shea, senior author of the paper, says the venom – a “complex toxic cocktail” evolved over millennia to stay ahead of prey’s own adaptive strategies – is absorbed onto the surface of nanoparticles in the new material and is permanently held there. This diverted it from doing any harm.

Thanks to the use of readily available, nonpoisonous components, the “nanodote” has a long shelf life and costs far less than traditional anti-venoms.

“Our treatment costs pennies on the dollar and, unlike the current one, requires no refrigeration,” O’Brien said. “It feels pretty great to think this could save lives.”

Since publishing their findings, the researchers have discovered that scorpion and spider-bite infections may also be slowed or stopped via their invention.

They have patents pending and are seeking public and private funding to move forward with clinical trials and product development.

Additionally, Shea’s group pioneered a synthetic antidote for bee melittin – the ingredient in stings that can kill people who have an allergic reaction – using similar methods.

“The goal is not to save mice from venom and bee stings,” Shea said, “but to demonstrate a paradigm shift in thinking about solutions to these types of problems. We have more work to do, and this is why we’re seeking a fairly significant infusion of resources.”

The US Department of Defense’s research arm financed the first phase of the laboratory work.

Shea said: “The military has platoons in the tropics and sub-Saharan Africa, and there are a variety of toxic snakes where they’re traipsing around.

“If soldiers are bitten, they don’t have a hospital nearby; they’ve got a medic with a backpack. They need something they can use in the field to at least delay the spread of the venom.”

In addition to the Defense Advanced Research Projects Agency, the National Science Foundation and the National Institutes of Health provided funding.

Snakebites kill about five people a year in the US.

Engineering the Protein Corona of a Synthetic Polymer Nanoparticle for Broad-Spectrum Sequestration and Neutralization of Venomous Biomacromolecules
Jeffrey O’Brien, Shih-Hui Lee, Shunsuke Onogi, and Kenneth J. Shea
J. Am. Chem. Soc., 2016, 138 (51), pp 16604–16607 DOI: 10.1021/jacs.6b10950


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