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

SARS-CoV-2 S 蛋白刺突片段对斑马鱼的毒性:一种研究其对人类健康危害的工具?

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作者:Bianca H Ventura Fernandes, Natália Martins Feitosa, Ana Paula Barbosa, Camila Gasque Bomfim, Anali M B Garnique, Ivana F Rosa, Maira S Rodrigues, Lucas B Doretto, Daniel F Costa, Bruno Camargo-Dos-Santos, Gabrielli A Franco, João Favero Neto, Juliana Sartori Lunardi, Marina Sanson Bellot, Nina Pach

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.

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