Proteomic and Phosphoproteomic Profiling of Kidney in Rhesus Macaques With SARS-CoV-2 Infection.

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.