Efficacy of the bothropic antivenom from Butantan Institute: obtention, characterization and neutralization of serinepeptidases from the venom of Bothrops jararaca

• Grant number: 13/15344-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2013
• End date: August 31, 2017
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Fernanda Calheta Vieira Portaro
• Grantee: Alexandre Kazuo Kuniyoshi
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The snake bite poisoning represents a public health issue for many countries in the world and in 2009 was recognized by the WHO as a neglected tropical condition. The genus Bothrops is considered the most important one in cases of snake bite poisoning in Brazil and, like other snakes, their venom is a complex mixture of components that act on different targets in the prey / victim. Taking in account that proteolytic enzymes from the classes of serine peptidases and metallopeptidases are the main toxins present in the venom of B. jararaca (about 65% of the composition of the venom), this work will focus on those components. Previous studies have shown that at least two serine peptidases, identified by mass spectrometry and still not yet characterized in the venom of B. jararaca, are not fully neutralized by the antivenom from Butantan Institute, and therefore the causes of these flaws should be investigated in this PhD project. We intend to evaluate by immunochemistry assays the ability of recognition of serine peptidases not neutralized by the commercial antivenom. Also, we intend to evaluate the immunogenicity of these peptidases, obtaining experimental sera specific for these molecules in rabbits as animal models. Thus, we believe that it is essential from the point of view of public health and biotechnology, investigate failures in commercial serum and suggest possible solutions. Another important fact that led us to write this project is purify the enzyme responsible for the chymotrypsin-like degrading activity of angiotensin I shown by our group in previous studies and that was partially blocked by the commercial antivenom. This new enzyme seems to belong to a class of serine peptidases undescribed in snake venoms. Thus, several chromatographic steps will be used to obtain the pure protein in order to characterize it. (AU)

Scientific publications

(6)

(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)

LOPES, PRISCILA HESS; ROCHA, MARISA M. T.; KUNIYOSHI, ALEXANDRE KAZUO; VIEIRA PORTARO, FERNANDA CALHETA; GONCALVES, LUIS ROBERTO C.. Edema and Nociception Induced by Philodryas patagoniensis Venom in Mice: A Pharmacological Evaluation with Implications for the Accident Treatment. Journal of Pharmacology and Experimental Therapeutics, v. 361, n. 3, p. 349-354, JUN 1 2017. (15/17053-5, 13/15344-7)

AMADEU MEGALE, ANGELA ALICE; MAGNOLI, FABIO CARLOS; KUNIYOSHI, ALEXANDRE KAZUO; IWAI, LEO KEI; TAMBOURGI, DENISE V.; PORTARO, FERNANDA C. V.; DA SILVA, WILMAR DIAS. Kn-Ba: a novel serine protease isolated from Bitis arietans snake venom with fibrinogenolytic and kinin-releasing activities. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 24, DEC 13 2018. (13/07467-1, 13/15344-7, 15/15364-3)

KUNIYOSHI, ALEXANDRE KAZUO; KODAMA, ROBERTO TADASHI; CAJADO-CARVALHO, DANIELA; IWAI, LEO KEI; KITANO, EDUARDO; FERNANDES DA SILVA, CRISTIANE CASTILHO; DUZZI, BRUNO; DA SILVA, WILMAR DIAS; PORTARO, FERNANDA CALHETA. Experimental antivenom against serine proteases from the Bothrops jararaca venom obtained in mice, and its comparison with the antibothropic serum from the Butantan Institute. Toxicon, v. 169, p. 59-67, NOV 2019. (15/13124-5, 13/07467-1, 13/15344-7, 12/06677-0, 15/15364-3)

CAJADO-CARVALHO, DANIELA; GALVAO, JULIANA; KUNIYOSHI, ALEXANDRE K.; CARNEIRO, PATRICIA DOS SANTOS; PAES LEME, ADRIANA FRANCO; PAULETTI, BIANCA ALVES; MARENGO, ELIANA BLINI; PORTARO, FERNANDA V.. Tityus serrulatus Scorpion Venom: In Vitro Tests and Their Correlation with In Vivo Lethal Dose Assay. TOXINS, v. 9, n. 12, DEC 2017. (15/15364-3, 13/15344-7, 13/15343-0, 09/54067-3)

ROBERTO TADASHI KODAMA; ALEXANDRE KAZUO KUNIYOSHI; CRISTIANE CASTILHO FERNANDES DA SILVA; DANIELA CAJADO-CARVALHO; BRUNO DUZZI; DOUGLAS CEOLIN MARIANO; DANIEL C. PIMENTA; RAFAEL BORGES; WILMAR DIAS DA SILVA; FERNANDA CALHETA VIEIRA PORTARO. A Kunitz-type peptide from Dendroaspis polylepis venom as a simultaneous inhibitor of serine and cysteine proteases. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, 2020-10-07. (15/13124-5, 11/02061-1, 13/15344-7, 13/07467-1, 15/15364-3)

KUNIYOSHI, ALEXANDRE KAZUO; KODAMA, ROBERTO TADASHI; FERREIRA MORAES, LUIS HENRIQUE; DUZZI, BRUNO; IWAI, LEO KEI; LIMA, ISMAEL FEITOSA; CAJADO-CARVALHO, DANIELA; PORTARO, FERNANDA VIEIRA. In vitro cleavage of bioactive peptides by peptidases from Bothrops jararaca venom and its neutralization by bothropic antivenom produced by Butantan Institute: Major contribution of serine peptidases. Toxicon, v. 137, p. 114-119, OCT 2017. (13/07467-1, 15/13124-5, 12/06677-0, 15/15364-3, 13/15344-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

KUNIYOSHI, Alexandre Kazuo. Efficacy of the antibothropic serum produced by Butantan Institute: obtaining, characterizing and neutralizing serinopeptidases of interest from the Bothrops jararaca venom.. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.