When the Cobra Bites, You’ll Be Glad Someone Sequenced Its Genome

https://www.nytimes.com/2020/01/09/science/cobra-venom-genome.html

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Scientists have sequenced the genome of one of the deadliest snakes in the world, the Indian cobra, and have taken a big step toward developing new and better treatments for their bites.

Although the Centers for Disease Control and Prevention estimates that thousands of people are bitten by snakes in the United States every year, few die from snake venom. But worldwide, snakebites lead to more than 400,000 amputations and 100,000 deaths a year.

Currently, antivenom is the only effective medicine, provided a bite victim can get treated in time. But producing the medicine is difficult.

First, venom has to be milked from the snake’s fangs, and it has to be done repeatedly to produce sufficient quantities. Then it must be injected into a large animal, usually a horse, to generate antibodies. The blood drawn from an infected horse has to go through a multiple-step process of purification to isolate its active ingredients.

The resulting antivenom contains many nonhuman antibodies irrelevant to venom, some of which can create harmful immune responses. Moreover, it is expensive. A vial of antivenom costs about $2,000, and treatment of one bite can require 25 vials or more. And in the end, the antivenom produced is not always effective in boosting the immune system of a snakebite victim.

Some scientists think genomic technologies could be used to synthesize antivenom, and eventually treat victims more cheaply and effectively. They want to study the venom genes themselves, including their organization, variability and evolution. Doing this requires mapping the snake’s genome.

In Nature Genetics on Monday, one team of researchers released their map of the genome of Naja naja, the Indian cobra. They found 12,346 genes expressed in the venom glands, what they call the “venom-ome” of the animal. Of these, they found 139 toxin genes, the ones that perform the biological reactions specific to toxins. Then they designated 19 of these genes as “venom-ome specific,” expressed only in the venom gland, and that are responsible for a wide range of symptoms in humans, including heart-function problems, paralysis, nausea, blurred vision, internal bleeding and death.

With this catalog of genes specific to venom production, they hope scientists can now begin to use recombinant protein technologies to generate antivenom effective against the venom of the Indian cobra and closely related species. As more snake genomes are completed, scientists may be able to combine species-specific toxins and create broad-spectrum antivenoms that could work against bites from multiple species.

The study’s senior author, Somasekar Seshagiri, a former staff scientist at Genentech and now president of SciGenom Research Foundation, a nonprofit research center in India, said that sequencing a snake’s genome can be done in less than a year for under $100,000.

“As much as we fear them, snakes are a remarkable product of evolution, present on every continent except Antarctica, and they’ve been around much longer than we have,” he said. “This will take some time, but we can now move toward modernizing the way we create antivenoms.”