Avaliação in sílico da interação de moléculas com potencial neuroprotetor na neurotoxina isolada do veneno de cascavel brasileira (Crotalus durissus terrificus)

Abstract

Ophidism is a public health problem classified in the category of Neglected Tropical Diseases according to the World Health Organization (WHO) because it does not arouse the interest of the pharmaceutical segments in research and development of drugs for more effective treatments in line with serum therapy, since most of occurrences are in regions where the population is socioeconomically vulnerable, without generating a profitable return for the industry. Snake venoms consist mainly of proteins, peptides and toxins that trigger various local and systemic effects on the victim. In crotalic poisoning, by the Brazilian rattlesnake, Crotoxin is one of the main toxins with neurotoxic action, that is, it causes neurological damage, leaving sequelae or leading to death. According to research in ethnobotany, studies have been intensified to explore secondary metabolites of medicinal plants such as flavonoids and cannabinoids with neuroprotective potential for neurological diseases such as seizures, epilepsy, Alzheimer's and Parkinson's disease. Therefore, the present study aimed to verify whether these neuroprotective properties are capable of inhibiting the action of the neurotoxin Crotoxin. To apply the Molecular Docking methodology, the crystallographic structures were obtained from the following free repositories: Protein Data Bank, Cannabis Database and Pubchem and the Openbabel converter. The preparation of the structures for docking was carried out in the Chimera off-line software and subsequently submitted to the Dockthor online platform for both the Blinding method and the Grid box, in silico tests were carried out to predict free energies in the receptor-ligand interaction, of the target Crotoxin with 28 ligands, including a reference drug (Surinan), ligands co-crystallised with bothrops moojeni toxins from the literature, flavonoids from Ocotea notata (Nees) and cannabinoids from Cannabis sativa. All steps of this procedure were performed on a personal computer with internet access. The results obtained showed promising interaction affinity values for the reference drug Surinan and for the cannabinoid Alfapinene, with scores -9.349 kcal/mol and -8.962 kcal/mol, respectively, demonstrating that they are good candidates for Crotoxin inhibitor drugs, intended for therapy complementary to the anticrotalic serum.