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Proteomic and Phosphoproteomic Profiling of Kidney in Rhesus Macaques With SARS-CoV-2 Infection
Yizhuo Tian1,2, Yanan Zhou3, Qiaochu Wang1
1State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
Abstract:
Coronavirus Disease 2019 (COVID-19) not only causes lung damage but also induces renal damage; however, there is currently no consensus on the key molecules and signaling pathways involved. Six rhesus macaques were divided into a control group and a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection group. Meanwhile, their kidneys were segmented into three regions: renal cortex (Cor), inner medulla (IM), and outer medulla (OM), and proteomics and phosphoproteomic analysis were conducted. Subsequently, we performed a comprehensive bioinformatics analysis to identify key molecules associated with COVID-19. We established proteomic and phosphoproteomic profiles of Cor, OM,and IM of kidneys infected with SARS-CoV-2. All regions exhibited varying intensities of inflammatory reactions and metabolic perturbations, implicating pathways such as the IL-17 signaling pathway and the RIG-I-like receptor signaling pathway. Immunohistochemistry confirmed the upregulation of proteins including ISG15, and S100A8/S100A9. By utilizing DrugBank, we identified 21 FDA-approved drugs targeting predicted kinases as candidates for treatment, which need to be verified in the future. This study provides a comprehensive data set and atlas of proteomics and phosphoproteomics of SARS-CoV-2 infected rhesus macaque kidneys.
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