Abstract
Envenoming caused by snakebites is considered a public health problem in many tropical and subtropical countries and has recently been included in the list of Neglected Tropical Diseases by the World Health Organization. In Latin America, the majority of ophidic accidents are caused by snakes from Bothrops and Crotalus genus. One of the main complications regarding bothropic envenomation is the prominent local muscle damage and subsequent neuromuscular transmission block, which is usually induced by phospholipase A2, an important component of these venoms. In this work, we propose for the first time, a broad structural and functional study of snake venom proteins - native, recombinant and complexed to potential inhibitors. The following techniques will be used: i) structural/biophysical: crystallography, small angle X-ray scattering, circular dichroism, dynamic light scattering, fluorescence and isothermal titration calorimetry, structural bioinformatics; ii) in vitro functional studies including electrophysiology, myographic techniques, real-time video-microscopy and radiochemical studies; iii) morphologic analysis (optic, confocal and electronic microscopy). This information could be very important for the identification, characterization and development (drug design) of substances with biotechnological and pharmacological usefulness. These compounds may be used for the control of symptoms that cannot be prevented or reverted by serum therapy administration and as aid for the treatment of the underlying pathological process. This project is aligned with other projects previously supported by FAPESP (four grants in the snake venom proteins field) and CNPq (three grants in the field) since 1997. Furthermore, the Brazilian laboratory was also supported by INCT in Toxinology (FAPESP/CNPq) and Toxinology project of the CAPES agency. The scientific output of the Brazilian laboratory in the snake venom toxin field accounts for more than 60 papers and 16 concluded theses in this field. Since 1991, the Laboratory do Pharmacology and Neurobiology, ICBAS-UPorto has done pioneering research in the study of the pathogenesis of neuromuscular transmission deficits, routinely using neurochemical, electrophysiological and bioimaging approaches such as those required for this project. Both Brazilian and Portuguese research groups have a fruitful collaborative project which includes a recently published paper within the frame of a post-doctoral grant by FAPESP (BEPE-FAPESP n° 2013/03624-5). (AU)
Scientific publications
(9)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FERNANDES, CARLOS A. H.;
MOREA, EDNA GICELA O.;
DOS SANTOS, GABRIEL A.;
DA SILVA, VITOR L.;
VIEIRA, MARINA ROVERI;
VIVIESCAS, MARIA ALEJANDRA;
CHATAIN, JEAN;
VADEL, AURELIE;
SAINTOME, CAROLE;
FONTES, MARCOS ROBERTO M.;
CANO, MARIA ISABEL NOGUEIRA.
A multi-approach analysis highlights the relevance of RPA-1 as a telomere end-binding protein (TEBP) in Leishmania amazonensis.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS,
v. 1864,
n. 7
JUL 2020.
Web of Science Citations: 0.
BOLDRINI-FRANCA, JOHARA;
PINHEIRO-JUNIOR, ERNESTO LOPES;
PEIGNEUR, STEVE;
PUCCA, MANUELA BERTO;
CERNI, FELIPE AUGUSTO;
BORGES, RAFAEL JUNQUEIRA;
COSTA, TASSIA RAFAELLA;
IMAI CARONE, SANTE EMMANUEL;
DE MATTOS FONTES, MARCOS ROBERTO;
SAMPAIO, SUELY VILELA;
ARANTES, ELIANE CANDIANI;
TYTGAT, JAN.
Beyond hemostasis: a snake venom serine protease with potassium channel blocking and potential antitumor activities.
SCIENTIFIC REPORTS,
v. 10,
n. 1
MAR 11 2020.
Web of Science Citations: 1.
CARDOSO, FABIO F.;
GOMES, ANTONIEL A. S.;
DREYER, THIAGO R.;
CAVALCANTE, WALTER L. G.;
DAL PAI, MAELI;
GALLACCI, MARCIA;
FONTES, MARCOS R. M.
Neutralization of a bothropic PLA(2)-like protein by caftaric acid, a novel potent inhibitor of ophidian myotoxicity.
Biochimie,
v. 170,
p. 163-172,
MAR 2020.
Web of Science Citations: 0.
CARDOSO, FABIO F.;
BORGES, RAFAEL J.;
DREYER, THIAGO R.;
SALVADOR, GUILHERME H. M.;
CAVALCANTE, WALTER L. G.;
DAL PAI, MAELI;
GALLACCI, MARCIA;
FONTES, MARCOS R. M.
Structural basis of phospholipase A(2)-like myotoxin inhibition by chicoric acid, a novel potent inhibitor of ophidian toxins.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS,
v. 1862,
n. 12,
p. 2728-2737,
DEC 2018.
Web of Science Citations: 4.
FERNANDES, CARLOS A. H.;
PAZIN, WALLANCE M.;
DREYER, THIAGO R.;
BICEV, RENATA N.;
CAVALCANTE, WALTER L. G.;
FORTES-DIAS, CONSUELO L.;
ITO, AMANDO S.;
OLIVEIRA, CRISTIANO L. P.;
FERNANDEZ, ROBERTO MORATO;
FONTES, MARCOS R. M.
Biophysical studies suggest a new structural arrangement of crotoxin and provide insights into its toxic mechanism.
SCIENTIFIC REPORTS,
v. 7,
MAR 3 2017.
Web of Science Citations: 9.
BORGES, RAFAEL J.;
CARDOSO, FABIO F.;
FERNANDES, CARLOS A. H.;
DREYER, THIAGO R.;
DE MORAES, DELKIA S.;
FLORIANO, RAFAEL S.;
RODRIGUES-SIMIONI, LEA;
FONTES, MARCOS R. M.
Functional and structural studies of a Phospholipase A(2)-like protein complexed to zinc ions: Insights on its myotoxicity and inhibition mechanism.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS,
v. 1861,
n. 1, A,
p. 3199-3209,
JAN 2017.
Web of Science Citations: 10.