Production, modification and characterization of animal toxins with potential biotechnological application

• Grant number: 19/10173-6
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2020
• End date: August 31, 2022
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Eliane Candiani Arantes Braga
• Grantee: Eliane Candiani Arantes Braga
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• City of the host institution: Ribeirão Preto
• Associated researchers: Iara Aimê Cardoso ; Karla de Castro Figueiredo Bordon

Abstract

Animal venoms and poisons constitute a rich source of substances with wide-ranging pharmacological activities. The bioprospecting of molecules from animal poisons and venoms combined with the use of biotechnological tools, such as the heterologous expression of toxins and the bioconjugation with polyethylene glycols (PEGs), allows the application of toxins in the development of new therapeutic strategies with better pharmacokinetic behavior and lower immunogenicity. In addition, the study of animal toxins helps to better understand the mechanism of toxicity of these molecules during the envenoming, enabling the development of more effective therapies and antivenoms. In this context, this proposal aims the bioprospecting of molecules from venoms from snakes Crotalus durissus terrificus and Crotalus durissus collilineatus and scorpion Tityus serrulatus with potential biotechnological application. Priority will be given to studies of serine proteases, vascular endothelial growth factors (VEGF), phospholipase A2 inhibitors (PLI), phosphodiesterases (PDE) and neurotoxins that act on voltage-gated sodium or potassium channels, using modern approaches of heterologous production, PEGylation and structural and functional characterization. These studies of components from different animal venoms aim to explore the therapeutic potential of toxins for the development of new drugs. (AU)

Scientific publications

(18)

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

FIGUEIREDO BORDON, KARLA DE CASTRO; COLOGNA, CAMILA TAKENO; FORNARI-BALDO, ELISA CORREA; PINHEIRO-JUNIOR, ERNESTO LOPES; CERNI, FELIPE AUGUSTO; AMORIM, FERNANDA GOBBI; PINO ANJOLETTE, FERNANDO ANTONIO; CORDEIRO, FRANCIELLE ALMEIDA; WIEZEL, GISELE ADRIANO; CARDOSO, IARA AIME; et al. From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery. FRONTIERS IN PHARMACOLOGY, v. 11, JUL 24 2020. (17/14035-1, 17/00586-6, 18/14158-9, 19/10173-6, 18/21233-7, 17/04724-4, 13/26619-7, 16/04761-4, 17/03580-9, 13/26200-6)

MARTINS, JONAS GAMA; SANTOS, GABRIELLE CRISTINA; DE LIMA PROCOPIO, RUDI EMERSON; ARANTES, ELIANE CANDIANI; FIGUEIREDO BORDON, KARLA DE CASTRO. Scorpion species of medical importance in the Brazilian Amazon: a review to identify knowledge gaps. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 27, SEP 20 2021. (19/10173-6, 19/27544-7)

CERNI, FELIPE; OLIVEIRA, ISADORA; CORDEIRO, FRANCIELLE; BORDON, KARLA; FERREIRA, ISABELA; MONTEIRO, WUELTON; ARANTES, ELIANE; CUNHA, THIAGO; PUCCA, MANUELA. The nociceptive response induced by different classes of Tityus serrulatus neurotoxins: The important role of Ts5 in venom-induced nociception. PLoS Neglected Tropical Diseases, v. 17, n. 1, p. 14-pg., 2023-01-01. (20/13176-3, 19/10173-6, 13/08216-2)

OLIVEIRA, ISADORA; COSTA, VICTOR; VERAS, FLAVIO; FERREIRA, ISABELA; CUNHA, FERNANDO; CUNHA, THIAGO; MONTEIRO, WUELTON; ARANTES, ELIANE; PUCCA, MANUELA. A Promising Biomolecule Able to Degrade Neutrophil Extracellular Traps: CdcPDE, a Rattlesnake Phosphodiesterase. TOXINS, v. 15, n. 1, p. 5-pg., 2023-01-01. (20/13176-3, 19/10173-6, 13/08216-2)

BERNARDES, CAROLINA PETRI; PINHEIRO-JUNIOR, ERNESTO LOPES; FERREIRA, ISABELA GOBBO; DE OLIVEIRA, ISADORA SOUSA; DOS SANTOS, NEIFE APARECIDA GUINAIM; SAMPAIO, SUELY VILELA; ARANTES, ELIANE CANDIANI; DOS SANTOS, ANTONIO CARDOZO. Fraction of C. d. collilineatus venom containing crotapotin protects PC12 cells against MPP plus toxicity by activating the NGF-signaling pathway. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 30, p. 14-pg., 2024-06-14. (15/24808-2, 19/10173-6, 11/23236-4)

DE OLIVEIRA, ISADORA SOUSA; PUCCA, MANUELA BERTO; WIEZEL, GISELE ADRIANO; CARDOSO, IARA AIME; FIGUEIREDO BORDON, KARLA DE CASTRO; SARTIM, MARCO AURELIO; KALOGEROPOULOS, KONSTANTINOS; AHMADI, SHIRIN; BAIWIR, DOMINIQUE; NONATO, MARIA CRISTINA; et al. Unraveling the structure and function of CdcPDE: A novel phosphodiesterase from Crotalus durissus collilineatus snake venom. International Journal of Biological Macromolecules, v. 178, p. 180-192, MAY 1 2021. (17/00586-6, 17/03580-9, 19/10173-6, 11/23236-4, 18/21233-7)

WIEZEL, GISELE A.; OLIVEIRA, ISADORA S.; FERREIRA, ISABELA G.; BORDON, KARLA C. F.; ARANTES, ELIANE C.. Hyperglycosylation impairs the inhibitory activity of rCdtPLI2, the first recombinant beta-phospholipase A₂ inhibitor. International Journal of Biological Macromolecules, v. 280, p. 12-pg., 2024-09-22. (21/11936-3, 09/54098-6, 19/10173-6, 20/13176-3, 17/00586-6)

FERREIRA, ISABELA; OLIVEIRA, ISADORA; BORDON, KARLA; REIS, MOUZARLLEM; WIEZEL, GISELE; SANCHEZ, CAROLINE; SANTOS, LUISA; SANTOS-FILHO, NORIVAL; PUCCA, MANUELA; ANTUNES, LUSANIA; et al. Beyond Angiogenesis: The Multitasking Approach of the First PEGylated Vascular Endothelial Growth Factor (CdtVEGF) from Brazilian Rattlesnake Venom. TOXINS, v. 15, n. 8, p. 21-pg., 2023-08-01. (20/13176-3, 21/11936-3, 17/00586-6, 19/10173-6)

DE OLIVEIRA NEVES, VIVIANO GOMES; DE MELLO, MARCELA M. BLASCKE; RODRIGUES, DANIEL; PERNOMIAN, LAENA; DE OLIVEIRA, ISADORA SOUSA; PARENTE, JULIANA M.; ARANTES, ELIANE CANDIANI; TOSTES, RITA C.; CASTRO, MICHELE M.. Type I collagen proteolysis by matrix metalloproteinase-2 contributes to focal adhesion kinase activation and vascular smooth muscle cell proliferation in the aorta in early hypertension. VASCULAR PHARMACOLOGY, v. 152, p. 9-pg., 2023-10-01. (19/10173-6, 20/13176-3, 19/09174-8)

CAROLINA PETRI BERNARDES; ERNESTO LOPES PINHEIRO JUNIOR; ISABELA GOBBO FERREIRA; ISADORA SOUSA DE OLIVEIRA; NEIFE APARECIDA GUINAIM DOS SANTOS; SUELY VILELA SAMPAIO; ELIANE CANDIANI ARANTES; ANTONIO CARDOZO DOS SANTOS. Fraction of C. d. collilineatus venom containing crotapotin protects PC12 cells against MPP + toxicity by activating the NGF-signaling pathway. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 30, 2024-06-14. (19/10173-6, 11/23236-4, 20/13176-3)

OLIVEIRA, ISADORA; FERREIRA, ISABELA; JACOB, BEATRIZ; CARDENAS, KIARA; CERNI, FELIPE; BAIA-DA-SILVA, DJANE; ARANTES, ELIANE; MONTEIRO, WUELTON; PUCCA, MANUELA. Harnessing the Power of Venomous Animal-Derived Toxins against COVID-19. TOXINS, v. 15, n. 2, p. 12-pg., 2023-02-01. (20/13176-3, 21/11936-3, 19/10173-6)

ALANO-DA-SILVA, NICOLY MALACHIZE; DE OLIVEIRA, ISADORA SOUSA; CARDOSO, IARA AIME; BORDON, KARLA DE CASTRO FIGUEIREDO; ARANTES, ELIANE CANDIANI. Exploring high molecular weight components in Tityus serrulatus venom. Toxicon, v. 255, p. 5-pg., 2025-01-17. (20/13176-3, 19/10173-6, 21/11547-7, 21/11936-3, 22/08964-8)

LOUREIRO, ELISA NAOMI SUZUKI DE ANDRADE; CORDEIRO, FRANCIELLE ALMEIDA; WIEZEL, GISELE ADRIANO; SANTOS-FILHO, NORIVAL ALVES; NUNES, CATARIN LETICIA; POLIZELLO, ANA CRISTINA MORSELI; AIRES, CAROLINA PATRICIA; ARANTES, ELIANE CANDIANI. Isolation, characterization, and peptide synthesis of fragments from the first phospholipase A2 identified in Rhinella diptycha toad poison. Toxicon, v. 269, p. 7-pg., 2026-01-01. (18/12026-8, 19/10173-6, 17/00586-6, 23/11311-9)

WIEZEL, GISELE ADRIANO; OLIVEIRA, ISADORA SOUSA DE; ARANTES, ELIANE CANDIANI. Simplifying traditional approaches for accessible analysis of snake venom enzymes. Toxicon, v. 255, p. 5-pg., 2025-01-22. (20/13176-3, 17/00586-6, 21/11936-3, 19/10173-6)

ISADORA SOUSA DE OLIVEIRA; NICOLY MALACHIZE ALANO-DA-SILVA; ISABELA GOBBO FERREIRA; FELIPE AUGUSTO CERNI; JACQUELINE DE ALMEIDA GONÇALVES SACHETT; WUELTON MARCELO MONTEIRO; MANUELA BERTO PUCCA; ELIANE CANDIANI ARANTES. Understanding the complexity of Tityus serrulatus venom: A focus on high molecular weight components. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 30, 2024-01-22. (21/11936-3, 21/11547-7, 22/08964-8, 19/10173-6, 20/13176-3)

GABRIELA DE OLIVEIRA ALMEIDA; ISADORA SOUSA DE OLIVEIRA; ELIANE CANDIANI ARANTES; SUELY VILELA SAMPAIO. Snake venom disintegrins update: insights about new findings. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 29, 2023-09-18. (22/04804-6, 20/13176-3, 22/08964-8, 20/15670-5, 22/05554-3, 21/11936-3, 19/10173-6)

ABREU, CAIO B.; BORDON, KARLA C. F.; CERNI, FELIPE A.; OLIVEIRA, ISADORA S.; BALENZUELA, CARLA; ALEXANDRE-SILVA, GABRIEL M.; ZOCCAL, KARINA F.; REIS, MOUZARLLEM B.; WIEZEL, GISELE A.; PEIGNEUR, STEVE; et al. Pioneering Study onRhopalurus crassicaudaScorpion Venom: Isolation and Characterization of the Major Toxin and Hyaluronidase. FRONTIERS IN IMMUNOLOGY, v. 11, AUG 20 2020. (17/00586-6, 16/04761-4, 17/04724-4, 17/03580-9, 19/10173-6, 17/14035-1, 18/21233-7)

FERREIRA, ISABELA GOBBO; PUCCA, MANUELA BERTO; CARDOSO, IARA AIME; FIGUEIREDO BORDON, KARLA DE CASTRO; WIEZEL, GISELE ADRIANO; AMORIM, FERNANDA GOBBI; RODRIGUES, RENATA SANTOS; RODRIGUES, VERIDIANA DE MELO; DE CAMPOS BRITES, VERA LUCIA; ROSA, JOSE CESAR; et al. Insights into structure and function of CdcVEGFs, the vascular endothelial growth factor from Crotalus durissus collilineatus snake venom. Biochimie, v. 200, p. 11-pg., 2022-09-01. (11/23236-4, 17/00586-6, 19/10173-6)