Effects of inhibitor molecules in toxins involved to muscular necrosis in botropic accidents

• Grant number: 21/14841-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2022
• End date: February 21, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Marcos Roberto de Mattos Fontes
• Grantee: Ivan Rossi Moraes
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Envenoming involving snakes from Bothrops genus can be considered a public health and social problem in Brazil, due their prominent local muscle damages, which can lead to limb amputation. Some proteins presented in bothropic venom are directly related to myonecrosis, including different classes of proteinases, phospholipases A2 (PLA2s), PLA2-like toxins and L-amino acid oxidases, that act directly in the muscle tissues cells. Considering that effects are not fully reverted by the antiophidic serum administration, is essential the search for new molecules to complement the antivenom therapy. Here, we propose the biochemical (In vivo and In vitro studies) and biophysical (protein crystallography, spectroscopy and microcalorimetry) with the toxin classes PLA2 and PLA2-like, and bioinformatics (docking and molecular dynamics simulation) using the all proteins classes presented in bothropic venom and inhibitors. The results obtained here can led to observe the possible modifications in the protein structure by the inhibitor molecules and also, better comprehend the structural basis of the inhibitor binding to venom proteins. We propose to identify the possibility of known inhibitors molecules that will work simultaneously in different classes of toxins.