In a feat that may go a long way in reducing mortality and disability from snake bites, a team of Indian researchers and their collaborators abroad have sequenced the genome of the highly poisonous Indian cobra.

The findings, published in the journal Nature Genetics on Monday, make Indian cobra the first among the most venomous four Indian snakes, which are collectively called the infamous “big four”, to be genetically mapped. The Indian cobra, together with the common krait, Russell’s viper and saw scaled viper, accounts for nearly 46,000 snake bite deaths in the country every year. Worldwide, 5.4 million snake bites occur every year, with 2.8 million of them in India. They are responsible for 4,00,000 disabilities globally, of which 1,38,000 are from India.

Using a mix of cutting-edge genomic technologies, the scientists, led by Sekar Seshagiri, President of the Chennai-based SciGenome Research Foundation (SGRF), have assembled the most contiguous genome of the cobra.

In the present study, researchers found that the Indian cobra genome has 19 key toxin genes, primarily expressed in the venom glands of the snake. “Targeting these toxins using synthetic human antibodies should lead to a safe and effective anti-venom for treating Indian cobra bites,” said Seshagiri. “If we get one good antivenom against the Indian cobra and genome sequences from the other three, we can generate antibodies (antivenom) to those three and quickly make a broad anti-venom,: Seshagiri told BusinessLine.

Apart from Seshagiri’s team, scientists from SGRF’s AgriGenome Labs and MedGonome Labs, US firm Genentech, Wayanad Wildlife Sanctuary in Kerala and their peers from many universities in the US and Singapore participated in the study.

Outdated procedure

Currently, antivenom is produced by immunising horses with extracted snake venom and is based on a process developed over 100 years ago. This process is laborious and suffers from a lack of consistency leading to varying efficacy and serious side-effects.

“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,” said R Manjunatha Kini, Professor, National University of Singapore (NUS), Singapore and an author of the study. Venom is also a great 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.

Universal antivenom

“The Indian cobra is the first of the ‘big four’ deadly snakes to be sequenced. This is a major step towards understanding its venom components and it will effectively change the way antivenom is developed,” said George Thomas, Chief Operating Officer, AgriGenome Labs.

The scientists said that the next step would be to use this genomic blueprint for venom toxins to make recombinant proteins, generate neutralising antibodies and test them in the clinic. Further, sequencing other snake genomes and venom glands will provide information on additional toxins from these snakes that need to be targeted, leading eventually to a universal antivenom.

“We believe a synthetic humanised antivenom can be produced in less than 2-3 years and tested in trials rapidly,” they said.

Karthik Sunagar, a researcher with the Indian Institute of Science, Bengaluru, said: “This is the first genome of an Indian snake that has been sequenced with the state-of-the-art sequencing technologies. This high-quality genome will not only be a wonderful resource for understanding the evolution of this medically important snake and its venom repertoire but can also be very useful for the innovation of next generation recombinant antivenoms.”

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