MOSCOW, March 4, Tatyana PichuginaResearchers have discovered a molecule that protects against a deadly toxin. This will help develop a new effective antidote. How the discovery will be implemented is in the material .
The most advanced weapon
Of all the poisonous animals on Earth, snakes are the largest. About four hundred of the three and a half thousand species are dangerous to humans. There are six in Russia.
Every year, about two million people suffer from reptiles on all continents except Antarctica. More than a hundred thousand die, mostly in poor regions of Africa, Asia, and Latin America. This number is growing, and there are no new effective antidotes. That is why in 2017, WHO added poisonous snake bites to the list of neglected tropical diseases.
The poison, which helps the reptile to hunt successfully, is synthesized in the body and injected through ducts in the teeth connected to the gland. Some of the most dangerous snakes are tree mambas, found in sub-Saharan Africa. Their venom consists of polypeptides aimed at different targets in the victim's body. Not all of their functions have been studied; new components are constantly being discovered. For example, mambalgins, which have an analgesic effect, and hemotoxic mambins were isolated from the secretion of black mambas.
< br />Unlike vipers, mambas do not hold their prey, but they can bite several times. First, a tingling sensation is felt in the affected area, then poisoning rapidly develops. Within 45 minutes, a person dies if an antidote is not administered. For this purpose, serum from the blood of large animals is used. They are injected with small doses of poison until the defense system synthesizes antibodies that bind the toxins.
Most serums act against one or more similar toxins. In India, for example, they produce a polyvalent drug against the venom of four of the deadliest species: the spectacled snake, the Indian krait, the chained viper and the sand epha.
Antidotes do not always work; some can cause allergies and even anaphylactic shock, sometimes requiring very large doses. In recent years, the production of serums has been curtailed due to unprofitability; there are difficulties with delivery, since everything needs to be kept cold. In short, the development of an effective universal antidote is more relevant than ever.
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Find and synthesize
The reason why a universal serum has not yet been created is the exceptional complexity of the composition of snake venom. It is a mixture of proteins and peptides of different types, with a wide variety of structures, functions, and biological targets. Some are aimed at destroying the nervous system, others act locally, causing bleeding or, conversely, thrombosis. There are also those that are designed for better digestion of the prey in the stomach of the predator.
Each species of snake has a unique secretion composition, which is based on enzymes of many chemical families. It is impossible to neutralize all toxins. As animal studies have shown, this is not necessary: the risk of death can be significantly reduced if you act against several of the most harmful substances.
These are primarily “three-fingered” alpha neurotoxins, characteristic of all slates, including mambas and cobras. They block nicotinic acetylcholine receptors in muscle cells, causing flaccid neuromuscular paralysis and death by asphyxiation. Depending on the length of the protein sequence, they are divided into short and long.
If we assume that the key regions of polypeptides are very conservative, that is, they are preserved in all types of alpha neurotoxins, then one can select one neutralizing antibody for all. This strategy is used to develop antiviral drugs, including HIV. It is known that viruses mutate quickly, but certain parts of their genome do not change. They are the ones targeted by vaccines, which protect even against newly emerging variants.
In addition, this approach does not require immunization of animals — instead, the desired molecule can be synthesized.
Scientists from the USA, India and Great Britain took on this task. We analyzed data on long three-fingered alpha neurotoxins stored in a database of medically useful snakes. Out of 60 billion human antibodies, several were selected that recognize one region common to all. We synthesized them and chose the best option — 95Mat5. The effectiveness was tested on mice that were injected with natural venom from Asian and African snakes.
Now we have to find antibodies against other main components of venoms, in particular short alpha neurotoxins and phospholipases of slate snakes, metalloproteinases, and serine proteases of vipers, scientists note. A universal antidote will have four or five antibodies that are effective against the most dangerous types of toxins. You can add a variety of monoclonal antibodies to the “cocktail” that target the venoms of specific snakes.