Geneticists decipher cobra’s poison cocktail

  • A team of researchers has analyzed the toxins of the South Asian cobra based on their genetic make-up. 19 toxins are therefore at the center of the poison cocktail.
  • The findings are to be used to produce broadly effective antidotes.
  • More than 100,000 people die from snakebites every year.

Nausea, headache, dizziness, paralysis: Millions of people are bitten by poisonous snakes every year – with serious consequences: According to the World Health Organization (WHO ), more than 100,000 bite victims die each year from the poison, and up to 500,000 more suffer permanent damage such as loss of vision or amputations of limbs. This is mainly due to the fact that antidotes are often not available, but also because the composition of the snake venom is not precisely known.

An international team of researchers has now analyzed the toxins of the South Asian cobra in detail based on their genetic make-up. The results could not only enable the development of synthetic antibodies against snake venom, but also drugs against various diseases.

Of the more than 3,000 species of snakes, over 600 are poisonous, writes the team led by molecular biologist Somasekar Seshagiri from the Californian biotechnology company Genentech in the journalNature Genetics . By far the greatest number of deaths from snake bites are in Asia. In India alone, more than 46,000 people die each year from snake bites, mainly from four highly poisonous species: the chain viper (Daboia russelii), the common sand otter (Echis carinatus), the common krait (Bungarus caeruleus) and the – also known as the spectacled snake – South Asian cobra (well well).

Antidotes from horse blood

One problem is that antidotes are very expensive and often unavailable – especially in rural areas where most people are bitten. Such antivenomes are currently produced by administering snake venom to horses, for example, and then isolating antibodies from the animals’ blood serum. A second problem is that little is known about the exact composition of the toxins, which can vary even within a species.

With their study, the researchers working with Seshagiri are now aiming for a new concept. They want to precisely characterize the individual toxins of the species on the basis of the genetic make-up and summarize them in databases. This could be used to synthetically produce antidotes in the future and possibly even produce a broad spectrum antivenome, they emphasize.

In addition, the findings could lead to new drugs such as painkillers or blood pressure lowerers. “High quality venomous mexican black kingsnake¬†genomes will enable the creation of a comprehensive catalog of venom gland-specific toxin genes that can be used to develop synthetic antidotes or certain combinations,” they write.

The South Asian cobra has 139 venom genes

In connection with the poison glands, the researchers found 139 genes in the cobra genome that code for substances from 33 families of toxins. 96 of them have counterparts in the king cobra (Ophiophagus hannah), the remaining 43 do not.

19 toxins, which are produced by the poison glands, are therefore at the center of the poison cocktail. Noticeable among them are the total of 9 3-finger toxins (3FTxs), named after their tripartite form, which affect, among other things, partly on nerves, partly on the heart and partly on cells and tissue. These 3FTxs are mainly found in the poisonous snake family (Elapidae), which includes cobras, mambas, sea snakes and the extremely poisonous taipans.

The 139 toxin genes found are probably responsible for “a broad spectrum of symptoms, including disorders of the cardiovascular system, muscle paralysis, nausea, visual disturbances and systemic effects such as bleeding.”

A catalog that contains the toxin variations both within a species and across species is important for the production of a broadly effective antidote. In addition, synthetic humanized antibodies are much more effective and much more tolerable than those produced by horses.

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A catalog of snake venoms could pave the way for a broad spectrum antivenome

Guido Westhoff, chairman of the Serum-Depot Germany association, is impressed by the work. “To list the whole poison cocktail, which consists of many toxins, in full is groundbreaking,” he says. The zoologist is convinced that synthetically produced antidotes would be far more effective and at the same time more tolerable than the current antibodies taken from other mammals. These sometimes did not work in a very targeted manner and could cause side effects such as allergic reactions.

Martin Metz from the Berlin Charit√© speaks of a comprehensive analysis that could offer many possibilities. “It is important that someone deals with the topic,” says the dermatologist. “Snake bites are a huge global health problem that goes unnoticed.” It is true that humanized synthetic antibodies are better and more tolerable than the currently common antivenomes. However, it remains to be seen whether their production is also cheaper – as the authors claim. The toxin database targeted by the researchers is also interesting. “If you have a catalog of snake venoms and have a lot of toxins in multiple species, that would be one possibility for a broad spectrum antivenome.”

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