Proteomic and Phosphoproteomic Characteristics of Multiple Brain Regions in Rhesus Macaques After SARS-CoV-2 Infection.

The SARS-CoV-2 Omicron variant is more contagious than the original Alpha variant and can still cause neurological symptoms, including cognitive impairment. To gain a deeper understanding of the molecular mechanisms underlying these neurological effects, this study was conducted. Proteomic and phosphoproteomic analyses were carried out utilizing LC-MS/MS. Samples included brainstem, cerebellum, frontal lobe, occipital lobe, parietal lobe, and temporal lobe from SARS-CoV-2 Omicron-infected and noninfected control rhesus macaques. Infection with Omicron resulted in inflammatory responses across all six brain regions, and significant regional-specific molecular alterations were observed. Proteomic and phosphoproteomic analyses revealed extensive abnormalities in immune activation, synaptic function, DNA repair, and signaling pathways across different brain regions. We further predicted key kinases and identified candidate proteins with significantly altered expression. This study reveals region-specific inflammatory and signaling signatures in the brain following Omicron infection. The recognized kinases and proteins with abnormal regulation serve as potential candidates for drug discovery. This can aid in formulating new therapeutic approaches for neurological issues related to COVID-19.