Cobra genome secrets found, way to better antivenom

An international team, comprising several Indian researchers, on Monday reported high-quality sequencing of Indian Cobra genome, unlocking the secret code of its 'venome-ome' that carries 139 genes, out of which 19 are linked to venom-specific toxins.

The finding may help save thousands of lives in future as it opens up the doors to create better quality antivenoms in the laboratory using recombinant DNA technology.

Approximately 50 lakh people worldwide are bitten by venomous snakes every year, resulting in about 400,000 amputations and more than 100,000 deaths. In India, more than 46,000 individuals die annually due to the Big Four - Indian cobra, Russell's Viper, Saw-Scaled and Common Krait.

Since 1896, antivenom remains the standard treatment for snakebites though they trigger serious adverse responses and their ability to neutralise the venom is poorly understood. They are also costly in the developing world.

The genetic sequencing, on the other hand, could lead to the development of a safe and effective humanized antivenom, the scientists reported in Nature Genetics.

“Targeting these 19 specific toxins using synthetic human antibodies should lead to safe and effective anti-venom for treating Indian Cobra bites,” said lead author Sekar Seshagiri, president, SciGenom Research Foundation and a former staff scientist at Genentech.

Currently, antivenom is produced by immunizing horses with extracted snake venom and extracting the antibodies subsequently. Developed well over 100 years ago, the process is laborious and suffers from lack of consistency leading to varying efficacy and side effects.

Using the genome and gene expression data from 14 different cobra tissues, the authors found that 19 toxin genes are expressed exclusively in the venom gland and verified the presence of protein for 16 of these genes by using mass spectrometry. They also performed comparisons with the prairie rattlesnake and identified 15 toxin gene families unique to the Indian cobra.

“It is about time we modernise antivenom development by leveraging genomics, recombinant protein expression and synthetic antibody development technologies. The Indian cobra genome and the catalogue of target toxins are a blueprint needed to do this. For the first time, we now have a full list of venom-relevant toxin genes of the Indian cobra” said R Manjunatha Kini, professor, the National University of Singapore and a co-author the study.

Venom is primarily used by snakes to subdue their prey. But it is also a rich source of drug-like molecules. The Indian cobra genome is no exception and it codes for toxin molecules that can block pain, reduce blood pressure and prevent blood clotting, the scientists have shown.

Scientists now plan to create the gene-maps of other three common poisonous snakes of India besides deadly African snakes such as the black mamba, carpet viper and spitting cobras in order to create a larger catalogue of venom toxins for developing a safe and universal anti-venom for snakebite victims all over India, Africa and other neighbouring countries.