Structural and functional studies with Bothropstoxin-I, from Bothrops jararacussu snake venom, and caffeic acid derivates

Abstract

Envenoming involving Bothrops snakes stand out in Brazil and other Latin American countries, representing 90% of notifications. Botropic envenoming is characterized by intense local myonecrosis that is not effectlively neutralized by the only available treatment, i.e., the antivenom. As a result, in severe cases, this envenoming can lead to amputation of limbs, disabling the victim. The main responsibles for the myonecrosis development are proteins structurally similar to phospholipase A2 enzymes (PLA2s). Among these PLA2s, stand out the catalytically inactive variants that have a lysine residue at position 49 (Lys49-PLA2s). Thus, it is proposed the study structural of bothropstoxin-I (BthTX-I), a Lys49-PLA2 isolated from Bothrops jararacussu, by techniques of X-ray crystallography. In this study, we propose the study of the interaction between the BthTX-I and possible inhibitors, such as cinnamic acid, p-coumarin acid, ferulic acid, chlorogenic acid, caftaric acid and cichoric acid. Corroboration of the neutralizing activity of these inhibitors will be investigated by electrophysiological and morphological studies in mice neuromuscular preparations. This project is the continuation of studies performed by the candidate in his master's course, that investigated the role of compounds of similar origin to those proposed in this project in the activity of the PrTX-I, a toxin almost identical to BthTX-I. The results of these studies were published in an international journal of high impact and two others articles are currently in preparation.