Toxic potential analysis of proteases and peptides present in scorpion Tityus serrulatus venom and the blockage capacity of commercial antivenoms: Enhancing the knowledge of venom and its mechanism of action.

• Grant number: 15/15364-3
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2016
• End date: August 31, 2018
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Fernanda Calheta Vieira Portaro
• Grantee: Fernanda Calheta Vieira Portaro
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Carla Cristina Squaiella ; Wilmar Dias da Silva

Abstract

Currently, cases of scorpion accidents involving humans are considered a public health problem in Brazil, and the numbers of such accidents surpass the reported data with other venomous animals such as snakes and spiders. The scorpions from Tityus genus are mainly responsible for such situation and, among them, the Tityus serrulatus (yellow scorpion) is the most important. This relevance is due to a high toxicity of its venom and, along with its reproductive strategy (parthenogenesis) and its easy adaptation to urban centers, it contributes to the increase on number of accidents of medical importance. As other animal venoms, the T. serrulatus venom (TsV) is a complex mixture of components that acts on different targets in the prey/victim, wherein peptides that interacts with ion channels are consider the main components. Although much information about neurotoxins is available, the same cannot be said about the proteolytic and peptides components present in this venom. Our laboratory has already obtained four publications about the characterization of these components, and with every discovery, new questions arise. Of these, two main questions are intriguing us. The first is about the failure of commercial antivenoms (anti-scorpionic and anti-arachnid sera) on blocking proteolytic activities and probably on peptides activities present in the T. serrulatus venom. The second question is about the role of these components during the envenomation. In addition, this project also aims to expand our studies analyzing the possible cytotoxic and pro- or anti-inflammatory effects of synthetic peptides and proteases purified from TsV. Obtaining answers for these questions is our greatest motivation to prepare this research project. (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)

CAJADO-CARVALHO, DANIELA; KUNIYOSHI, ALEXANDRE KAZUO; DUZZI, BRUNO; IWAI, LEO KEI; DE OLIVEIRA, URSULA CASTRO; MEIRELLES JUNQUEIRA DE AZEVEDO, INACIO DE LOIOLA; KODAMA, ROBERTO TADASHI; PORTARO, FERNANDA VIEIRA. Insights into the Hypertensive Effects of Tityus serrulatus Scorpion Venom: Purification of an Angiotensin-Converting Enzyme-Like Peptidase. TOXINS, v. 8, n. 12, DEC 2016. (13/15343-0, 15/15364-3)

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)

CAJADO-CARVALHO, DANIELA; FERNANDES DA SILVA, CRISTIANE CASTILHO; KODAMA, ROBERTO TADASHI; CEOLIN MARIANO, DOUGLAS OSCAR; PIMENTA, DANIEL CARVALHO; DUZZI, BRUNO; KUNIYOSHI, ALEXANDRE KAZUO; PORTARO, FERNANDA VIEIRA. Purification and Biochemical Characterization of TsMS 3 and TsMS 4: Neuropeptide-Degrading Metallopeptidases in the Tityus serrulatus Venom. TOXINS, v. 11, n. 4, APR 2019. (13/15343-0, 15/15364-3)

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)

MANCUSO, RUBIA I.; MIYAJI, ELIANE N.; SILVA, CRISTIANE C. F.; PORTARO, FERNANDA V.; SOARES-SCHANOSKI, ALESSANDRA; RIBEIRO, ORLANDO G.; OLIVEIRA, MARIA LEONOR S.. Impaired expression of CXCL5 and matrix metalloproteinases in the lungs of mice with high susceptibility to Streptococcus pneumoniae infection. IMMUNITY INFLAMMATION AND DISEASE, v. 6, n. 1, p. 128-142, MAR 2018. (14/11087-2, 13/26052-7, 15/15364-3)

FERNANDES SILVA, CRISTIANE CASTILHO; MENEZES, MILENE CRISTINA; PALOMINO, MIRYAM; OLIVEIRA, ANA KARINA; IWAI, LEO KEI; FARIA, MARCELLA; PORTARO, FERNANDA VIEIRA. Peptides derived from plasma proteins released by bothropasin, a metalloprotease present in the Bothrops jararaca venom. Toxicon, v. 137, p. 65-72, OCT 2017. (14/02788-7, 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)