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With rattlesnake venom, research creates a molecule that regulates blood clotting

Publicado em 23 novembro 2021

The fauna and flora can “hide” a multitude of treatments that are unprecedented for science, as a team of researchers from Brazil and Belgium discovered when analyzing the poison of a rattlesnake, of the subspecies Crotalus durissus collilineatus. Found in snake toxin, the protein collinein-1 went through some processes and became a molecule of pharmaceutical interest, being able to regulate blood clotting.

 

Published in the scientific journal International Journal of Biological Macromolecules, the study details how scientists worked on the rattlesnake venom protein, making it more stable in the body and resistant to the immune system. It is these increments that will allow for its potential commercial use. A synthetic version of the molecule is already being produced, but the process of developing new drugs must still be long.

Turbine Rattlesnake Toxin in Laboratory

“The technique aims to keep PEG-cholinein-1 circulating in the body for longer, which can reduce the interval between administrations if it becomes a drug. In addition, it reduces degradation by components of the human organism and improves its functional properties”, explained researcher Ernesto Lopes Pinheiro Júnior, first author of the article, to the FAPESP Agency.

The technique adopted by the researchers is known as pegylation and consists of adding polyethylene glycol (PEG) to the toxin’s molecule of interest. It is worth explaining that PEG reduces the interaction with the immune system and prevents the formation of aggregates that reduce the activity of the molecule by the body. At this stage, the protein is called PEG-collinein-1.

“Pegylation is quite common in the pharmaceutical industry. There are 19 drugs that use the technique already approved. This is the first time, however, that the method has been used on an animal toxin, in its recombinant form. [produzida em laboratório por um fungo geneticamente modificado]”, says Eliane Candiani Arantes, professor at the Faculty of Pharmaceutical Sciences of Ribeirão Preto at USP and supervisor of the study.

Protein actions in snake venom

Part of the rattlesnake’s venom, the protein collinein-1 consumes fibrinogen, a compound present in the blood responsible for clotting. In this way, it triggers a hemorrhage in those who are bitten by the snake, being an important element in both the animal’s attack and defense.

In addition to “natural” use, the researchers identified that, when isolated and administered in small doses, the protein can prevent the formation of thrombi that cause stroke, for example. Now, when it is applied directly to the skin (topical use), it can have the opposite effect. In this context, the protein stimulates blood clotting in wounds that are difficult to heal. Therefore, it also has great potential for use in dressings, the scientists point out.

However, a possible limitation for the applications of the rattlesnake venom protein would be its obtainment. This would require the maintenance of a large serpentarium, with professionals qualified to extract the venom. This barrier would hardly allow any derivative product to reach the market.

In previous studies, the researcher and co-author of the study, Johara Boldrini-França, managed to clone the gene that produces collinein-1. Then the team created a version of the yeast Pichia pastoris, that carries the snake gene, responsible for encoding the protein. “This strategy is widely used in the pharmaceutical industry. Part of the insulin produced today, for example, comes from yeasts that produce this human protein”, he explains.

Thus, the potential applications of the drug that regulates blood clotting already start with an advantage: the low production cost and the ability to be obtained on a large scale. Now, more studies should evaluate its applications as much. in vitro how much in vivo.

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