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Newly Sequenced Indian Cobra Genome Could Lead to Better Antivenoms

A genetic approach could circumvent the pitfalls associated with current antivenom synthesis techniques

The venomous Indian cobra (Naja naja) is one of the deadliest snakes in the world. (Public domain)
smithsonianmag.com

The secret to surviving a cobra bite isn’t ice or a tourniquet, and it certainly isn’t sucking venom out of an open wound. Instead, one of humankind’s most powerful weapons against these deadly encounters is modern genetics—the ability to sequence a snake’s genome and leverage venom-specific genes to synthesize an ideal antidote.

Now, a team of researchers has taken this exact strategy with the genome of the India cobra (Naja naja), one of the most dangerous snakes in the world. Their findings, published this week in Nature Genetics, reveals that at least 19 genes are responsible for cobra venom’s toxic effects—and could help lay the groundwork for a new generation of antivenoms that quickly and precisely render the products of these genes ineffective. Such breakthroughs are urgently needed, especially in India, where more than 46,000 people die every year from snake bites, reports Megan Molteni at Wired.

For more than a century, researchers have relied on a somewhat murky process to produce antivenoms: injecting small doses of venom into animals like rabbits or horses then harvesting and purifying the protective antibodies their bodies produce to neutralize the noxious substance. The laborious process of generating these animal-derived cocktails is error-prone and expensive. Even the final products carry their own drawbacks—they don’t always work, and can come with a bevy of nasty side effects, reports Nicholas Bakalar at the New York Times.

“The value of genomics is that it will allow us to produce medicines that are more concretely defined,” study author Somasekar Seshagiri, a geneticist and president of the SciGenom Research Foundation in Bangalore, tells Molteni. “Antivenoms will no longer just be like some magic potion we pull out of a horse.”

Taking a comprehensive genetic approach could circumvent these issues, Seshgari tells Molteni. After mapping out the contents of the cobra’s 38 chromosomes, the researchers identified more than 12,000 genes expressed in the animal’s venom glands. Of these, 139 played a role in the generation of the toxins themselves. A further subset of 19 genes appeared to be directly responsible for the venom’s most odious effects in people, such as paralysis, nausea, internal bleeding and, in some cases, death.

“Until now, [these venom-specific] areas of the snake genome have been total black boxes,” Todd Castoe, an evolutionary geneticist at the University of Texas at Arlington who was not involved in the work, tells Molteni.

Expressed in bacteria or yeast, these 19 genes could help researchers generate gobs of the proteins that make cobra venom pack its deadly punch. The proteins could then be bait for libraries of human antibodies, the most potent of which could become the ingredients for ultra-effective, ultra-precise antivenoms that react only to venom proteins, potentially minimizing side effects in people.

The findings also set the stage for similar work in other species of snakes, whose genomes can now be sequenced in less than a year for less than $100,000, Seshagiri tells Bakalar. If the world’s database of snake genomes continues to grow, researchers may someday have the tools to generate broad-spectrum antivenoms that can be deployed against bites from all sorts of unsavory creatures—without ever troubling a horse again.

About Katherine J. Wu
Katherine J. Wu

Katherine J. Wu is a Boston-based science journalist and Story Collider senior producer. She holds a Ph.D. in Microbiology and Immunobiology from Harvard University. Previously, she served as a Digital Editor at NOVA Next and was Smithsonian magazine's 2018 AAAS Mass Media Fellow.

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