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Deep dive in the deadly chemistry of snakebites

Danish and Costa Rican scientists are the first to test snake venom with the help of synthetic human proteins. The project has been carried out with funding from the Lundbeck Foundation.

If you want to resist an attack from a powerful opponent, it helps to know what weapon they use.

The better you understand their terrible and cunning trick, the easier it is – all things being equal – to choose good and effective countermeasures.

This is the thinking behind an article by a team of researchers from the Technical University of Denmark’s DTU Bioengineering and the University of Costa Rica recently published in the scientific journal Toxins.

 

The article is about snake venom – primarily from the viper – although not from Vipera berus, ‘the Danish viper’, which happens to be the only poisonous snake in the Nordic region. For while a close encounter with Vipera berus, can be extremely uncomfortable for a human, its bite is fortunately rarely deadly.

The same cannot be said of species like the Russell’s viper, Daboia russelli, which is found in countries such as Pakistan, India, Sri Lanka and Thailand. It is extremely toxic and wantonly kills both animals and humans – and the African puff adder, Bitis arietans, is not a hair better.

Globally, around 140,000 people die every year from snakebites – while a further 500,000 survive such a venom attack, but not without severe consequences and damage, which they will have to live with for the rest of their lives.

There are therefore very good reasons for gaining a better understanding of the chemistry of snake venom in order to develop effective antivenoms. This is the basic premise behind the Danish-Costa Rican project, in which scientists have successfully analysed snake venom using synthetic versions of human proteins.

 

A sharp bite

When a snake attacks, the bite seems to come from out of nowhere…followed by the pain from the sharp fangs and the effects of the toxic chemical cocktail that is now flowing through the victim’s veins. Snake venom can cause everything from internal haemorrhaging to tissue or cell death.

Through evolution, snakes the world over have fine-tuned their venom, and this biological development has primarily been concentrated in two groups of snake venom enzymes.

These enzymes are present in the venom of many snakes – especially vipers – and it is these enzymes that the Danish-Costa Rican team of researchers has examined, according to one team member, Associate Professor Andreas Laustsen from DTU Bioengineering.

Andreas Laustsen is one of the venomous snake experts the WHO consults – and in 2017, he received the Lundbeck Foundation’s Talent Prize for his research into the development of new types of antivenom against snakebites.

The new research article in Toxins deals with the team’s efforts to paint a detailed portrait of how and when snake venom actually attacks the human organism, says Andreas Laustsen:

‘We know that snakebites have a variety of consequences – like inner haemorrhaging and cell death – but the fact is, snake venom can have many more attack points than are immediately apparent. It is all these attack points that we are working to identify – because the more we understand these details, the greater the likelihood that we can develop the right antivenom. And thus save human lives.’

 

A tray of proteins 

The process of developing new types of antivenom often involves lab experiments in which scientists combine blood and snake venom. This makes it possible to study some of the reactions the toxin causes – but it is an extremely painstaking process in many ways, according to Andreas Laustsen:

‘That’s why we decided to see if we could find a different way – and skip the blood altogether. So we took venom from five vipers and one cobra, and tested them, species by species, by pouring them over a special “tray”. The tray was full of little “wells”, each containing synthetic copies of a wide range of different protein sequences from humans and selected animals – and with the help of ultraviolet light, we could see whether these proteins were cut into pieces when they were hit by the special snake venom enzymes.’

This allowed the scientists to detect where in the human organism – and in the selected animals – a specific snake venom causes damage. It also enabled them to see what damage it causes, explains Andreas Laustsen:

‘The method is actually very fast, and it can be used with all snake venoms. The little “trays” are not something we invented – it’s just the first time scientists have used trays of synthetic human and animal proteins to test snake venom.’

The Danish-Costa Rican team will now conduct similar analyses of the toxins from a number of other venomous snakes – and based on the data they collect, they hope it will be possible to develop a new type of antivenom says Andreas Laustsen:

‘Based on our results, it will be possible to develop tiny molecules – microscopic structures – that are similar to the protein sequences of humans, which the snake venom cuts into pieces. If the structures work as expected, they would act as a kind of “cork”, preventing the snake venom from entering vital functions and areas in the human body. Time will tell whether it works, but scientifically, it should be possible.”

’Protease Activity Profiling of Snake Venoms Using High-Throughput Peptide Screening’

The research behind the article in Toxins is funded by the Lundbeck Foundation and the Novo Nordisk Foundation.

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