oxicity of spike fragments SARS-CoV-2 S protein for zebrafish: A tool to study its hazardous for human health

Author(s):Show less -

Ventura Fernandes, Bianca H. ^[1] ; Feitosa, Natalia Martins ^[2] ; Barbosa, Ana Paula ^[3] ; Bomfim, Camila Gasque ^[3] ; Garnique, Anali M. B. ^[4] ; Rosa, Ivana F. ^[5] ; Rodrigues, Maira S. ^[5] ; Doretto, Lucas B. ^[5] ; Costa, Daniel F. ^[5] ; Camargo-dos-Santos, Bruno ^[6] ; Franco, Gabrielli A. ^[6] ; Favero Neto, Joao ^[6] ; Lunardi, Juliana Sartori ^[6] ; Bellot, Marina Sanson ^[6] ; Capelini Alves, Nina Pacheco ^[6] ; Costa, Camila C. ^[7] ; Aracati, Mayumi F. ^[7] ; Rodrigues, Leticia F. ^[7] ; Cirilo, Rafaela Hemily ^[7] ; Colagrande, Raul Marcelino ^[6] ; Gomes, Francisco I. F. ^[8] ; Nakajima, Rafael T. ^[5] ; Belo, Marco A. A. ^[9] ; Giaquinto, Percilia Cardoso ^[10] ; de Oliveira, Susana Luporini ^[11] ; Eto, Silas Fernandes ^[12] ; Fernandes, Dayanne Carla ^[13] ; Manrique, Wilson G. ^[14] ; Conde, Gabriel ^[15] ; Rosales, Roberta R. C. ^[16] ; Todeschini, Iris ^[17] ; Rivero, Ilo ^[18] ; Llontop, Edgar ^[17] ; Sgro, German G. ^{[17, 19]} ; Oka, Gabriel Umaji ^[17] ; Bueno, Natalia Fernanda ^[17] ; Ferraris, Fausto K. ^[20] ; de Magalhaes, Mariana T. Q. ^[21] ; Medeiros, Renata J. ^[22] ; Mendonca-Gomes, Juliana M. ^[23] ; Junqueira, Mara Souza ^[24] ; Conceicao, Katia ^[25] ; de Pontes, Leticia Gomes ^[26] ; Condino-Neto, Antonio ^[26] ; Perez, Andrea C. ^[27] ; Barcellos, Leonardo J. G. ^{[27, 28]} ; Correa Junior, Jose Dias ^{[29, 30]} ; Dorlass, Erick Gustavo ^[3] ; Camara, Niels O. S. ^[23] ; Durigon, Edison Luiz ^[3] ; Cunha, Fernando Q. ^[31] ; Nobrega, Rafael H. ^[5] ; Machado-Santelli, Glaucia M. ^[4] ; Farah, Chuck S. ^[17] ; Veras, Flavio P. ^{[32, 33]} ; Galindo-Villegas, Jorge ^[34] ; Costa-Lotufo, V, Leticia ; Cunha, Thiago M. ^{[32, 33]} ; Chammas, Roger ^[35] ; Carvalho, Luciani R. ^{[36, 37]} ; Guzzo, Cristiane R. ^[28] ; Malafaia, Guilherme ^[38] ; Charlie-Silva, Ives ^[39]

Affiliation:Show less -

^[1] Univ Sao Paulo, Lab Controle Genet & Sanitario, Diretoria Tecn Apoio Ensino & Pesquisa, Fac Med, Sao Paulo - Brazil

^[2] Univ Fed Rio de Janeiro UFRJ, Inst Biodiversidade & Sustentabilidade NUPEM, Lab Integrad Biociencias Translacionais LIBT, Macae, RJ - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Cell Biol, Sao Paulo - Brazil

^[5] Sao Paulo State Univ, Inst Biosci, Dept Morphol, Reprod & Mol Biol Grp, Botucatu, SP - Brazil

^[6] Sao Paulo State Univ, Inst Biosci Botucatu, Dept Struct & Funct Biol, Botucatu, SP - Brazil

^[7] Sao Paulo State Univ UNESP, Dept Prevent Vet Med, Jaboticabal - Brazil

^[8] Univ Sao Paulo, Ctr Res Inflammatory Dis, Ribeirao Preto Med Sch, Dept Pharmacol, Sao Paulo - Brazil

^[9] Brasil Univ, Descalvado, SP - Brazil

^[10] Univ Estadual Paulista, Inst Biociencias, Dept Fisiol, Sao Paulo - Brazil

^[11] Univ Estadual Paulista, Sao Paulo, SP - Brazil

^[12] Univ Fed Roraima, PROCISA, Postgrad Program Hlth Sci, Procisa - Brazil

^[13] Butantan Inst, Immunochem Lab, Sao Paulo - Brazil

^[14] Fed Univ Rondonia, Dept Vet Med, Aquaculture Hlth Lab, GRUPESA, LABSA, Rolim de Moura Campus, Rondonia - Brazil

^[15] Sao Paulo State Univ, Dept Prevent Vet Med, Jaboticabal - Brazil

^[16] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol, Ribeirao Preto - Brazil

^[17] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil

^[18] Pontificia Univ Catolica Minas Gerais, Belo Horizonte, MG - Brazil

^[19] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias BioMol, Ribeirao Preto, SP - Brazil

^[20] Fiocruz MS, Dept Pharmacol & Toxicol, Oswaldo Cruz Fdn, Rio De Janeiro - Brazil

^[21] Univ Fed Minas Gerais, Inst Biol Sci, Dept Biochem & Immunol, Belo Horizonte, MG - Brazil

^[22] Natl Inst Qual Control Hlth, Dept Pharmacol & Toxicol, Lab Physiol, INCQS Fiocruz Zebrafish Facil, Rio De Janeiro - Brazil

^[23] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Transplantat Immunobiol Lab, Sao Paulo - Brazil

^[24] Univ Sao Paulo, Fac Med, Ctr Translat Res Oncol, Canc Inst State Sao Paulo, Sao Paulo - Brazil

^[25] Univ Fed Sao Paulo, Lab Peptide Biochem, Sao Paulo - Brazil

^[26] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Human Immunol, Sao Paulo - Brazil

^[27] Univ Fed Santa Maria, Grad Program Pharmacol, Santa Maria, RS - Brazil

^[28] Univ Passo Fundo, Lab Fish Physiol, Grad Program Bioexpt & Environm Sci, Passo Fundo, RS - Brazil

^[29] LIQBRA, Lab Estudo Interacao Quim Biol & Reprod Anim, Bloco O3, 174, Sao Paulo - Brazil

^[30] Univ Fed Minas Gerais, Dept Morfol, Inst Ciencias Biol, Belo Horizonte, MG - Brazil

^[31] Univ Sao Paulo, Ctr Res Inflammatory Dis, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil

^[32] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto, SP - Brazil

^[33] Univ Sao Paulo, Ctr Res Inflammatory Dis, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

^[34] Nord Univ, Fac Biosci & Aquaculture, N-8049 Bodo - Norway

^[35] Univ Sao Paulo, Ctr Invest Translac Oncol, Inst Canc Estado Sao Paulo, Fac Med, Sao Paulo - Brazil

^[36] Dept Clin Med, Discipline Endocrinol, Sao Paulo - Brazil

^[37] LIM 42, Lab Hormonios & Genet Mol, Sao Paulo - Brazil

^[38] Goiano Fed Inst, Biol Res Lab, Urutai Campus, Urutai - Brazil

^[39] Costa-Lotufo, Leticia, V, Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Science of The Total Environment; v. 813, MAR 20 2022.
• Web of Science Citations: 0

Abstract

Despite the significant increase in the generation of SARS-CoV-2 contaminated domestic and hospital wastewater, little is known about the ecotoxicological effects of the virus or its structural components in freshwater vertebrates. In this context, this study evaluated the deleterious effects caused by SARS-CoV-2 Spike protein on the health of Danio rerio, zebrafish. We demonstrated, for the first time, that zebrafish injected with fragment 16 to 165 (rSpike), which corresponds to the N-terminal portion of the protein, presented mortalities and adverse effects on liver, kidney, ovary and brain tissues. The conserved genetic homology between zebrafish and humans might be one of the reasons for the intense toxic effects followed inflammatory reaction from the immune system of zebrafish to rSpike which provoked damage to organs in a similar pattern as happen in severe cases of COVID-19 in humans, and, resulted in 78,6% of survival rate in female adults during the first seven days. The application of spike protein in zebrafish was highly toxic that is suitable for future studies to gather valuable information about ecotoxicological impacts, as well as vaccine responses and therapeutic approaches in human medicine. Therefore, besides representing an important tool to assess the harmful effects of SARS-CoV-2 in the aquatic environment, we present the zebrafish as an animal model for translational COVID-19 research. (AU)

• FAPESP's process: 19/00195-2 - Understanding the c-di-GMP signaling networks and the Type II secretion system present into the human pathogen Leptospira interrogans Copenhageni
• Grantee: Cristiane Rodrigues Guzzo Carvalho
• Support Opportunities: Regular Research Grants
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• Grantee: Leticia Veras Costa Lotufo
• Support Opportunities: Regular Research Grants
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• Grantee: Eduardo Maffud Cilli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/17303-7 - Structure and function of bacterial secretion systems
• Grantee: Shaker Chuck Farah
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/04680-0 - Design of different fragments of SARS-CoV-2 surface protein spike for the development of fast diagnostic test and vaccine
• Grantee: Cristiane Rodrigues Guzzo Carvalho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/04294-1 - Structural and functional studies of the Xanthomonas citri Type IV Secretion System
• Grantee: Germán Gustavo Sgro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/21739-0 - Antimicrobial activity of proteins secreted by Xanthomonas citri against microorganisms of medical interest
• Grantee: Camila Gasque Bomfim
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 19/19939-1 - Effects of marine pharmaceuticals in ZFL cell line
• Grantee: Ives Charlie da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/18356-2 - Expression and purification of the GspC-GspD complex of the type II secretion system of Leptospira interrogans Copenhgeni
• Grantee: Natalia Fernanda Bueno
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
• FAPESP's process: 19/14285-3 - Role of succinate/SUCNR1 signalling pathway in sensory neurons in neuropathic pain development
• Grantee: Francisco Isaac Fernandes Gomes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/12234-2 - Isolation and structural studies on the Xanthomonas citri Type IV pilus and T4SS pilus
• Grantee: Edgar Enrique Llontop Cornejo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral