This week, an international team of researchers reported that they have sequenced the genome of the Indian cobra, in the process identifying the genes that define its venom. This, they hope, can provide a blueprint for developing more effective antivenom.
Are existing antivenoms not effective enough?
Their efficacy varies, besides producing side effects. In India, the challenge has been producing antivenom for the species known collectively as the “big four” — the Indian cobra (Naja naja), common krait (Bungarus caeruleus), Russell’s viper (Daboia russelii), and saw-scaled viper (Echis carinatus). A common antivenom is marketed for the treatment of bites from the “big four”, but its effectiveness came under question in a study published last month (not connected to the one that sequenced the cobra genome). While the common antivenom worked as marketed against the saw-scaled viper and the common cobra, it fell short against some neglected species and also against one of the “big four” — the common krait.
Accidental contact with snakes lead to over 100,000 deaths across the world every year. India alone accounts for about 50,000 deaths annually, and these are primarily attributed to the “big four”.
So, there are two different studies?
This week’s paper is the first one to describe the cobra genome. It is a multinational study by 42 authors, including from India, and is published in Nature Genetics. It is led by Dr Sekar Seshagiri, president of the nonprofit SciGenom Research Foundation based in Bengaluru. The other study, while unrelated, also deals with antivenom. Published in PLOS Neglected Tropical Diseases last month, it is ed by Professor Kartik Sunagar of IISc Bengaluru; other authors include the herpetologist Romulus Whitaker.
Why has production of effective antivenom been challenging?
Venom is a complex mixture of an estimated 140-odd protein or peptides. Only some of these constituents are toxins that cause the physiological symptoms seen after snakebite. But antivenom available today does not target these toxins specifically. Antivenom is currently produced by a century-old process — a small amount of venom is injected into a horse (or a sheep), which produces antibodies that are then collected and developed into antivenom.
This is expensive, cumbersome and comes with complications. Some of the antibodies raised from the horse may be completely irrelevant. The horse also has a lot of antibodies floating in its blood that have nothing to do with the venom toxins. “One more problem with horse antibodies — our immune system recognises it as foreign and when antivenom is given our body mounts an antibody response… This leads to what is called serum sickness,” lead author Seshagiri told The Indian Express. “Also, next time if one is unlucky and has a snakebite incident (even if it is a different snake) and they are given a horse-derived antivenom, the body is going to have a severe allergic reaction.”
How does decoding the genome help?
In the Indian cobra genome, the authors identified 19 key toxin genes, the only ones that should matter in snakebite treatment. They stress the need to leverage this knowledge for creation of antivenom using synthetic human antibodies. “Targeting these 19 specific toxins using synthetic human antibodies should lead to a safe and effective antivenom for treating Indian cobra bites,” Seshagiri said. And the logical next step would be obtaining the genomes and the venom gland genes from the other three of the “big four” (as well as deadly African species), leading to a possible common antivenom against bites from all four.
Is genomics the only way forward?
Sunagar, who led the other study, is part of an international consortium, funded by the UK Department for International Development, and looking to develop new-generation antivenom. “… We are trying to produce highly specific antibodies to counter the toxic effects of snake venoms. The aim is to produce antibodies that are broadly effective, not only against snake venoms in India but also in the sub-Saharan Africa,” he told The Indian Express.
Asked about the cobra genome sequence, Sunagar said it is of really high quality. “Sequence information of the genes that code for venom proteins is very important for the production of recombinant antivenoms. However, there is a very long way to go from genomes to effective anti-snake venoms.”
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