Investigating Molecular Aspects of Sars-Cov-2 Neurological Manifestations, a Systems Biology Approach Publisher



M Mozafar MARYAM ; Sa Mirmotalebisohi Seyed AMIR ; Ar Shahverdi Ahmad REZA ; H Zali HAKIMEH
Source: Human Gene Published:2025

Abstract

Objectives: Amid the COVID-19 pandemic, reported neurological symptoms and potential syndromes such as ischemic stroke, seizure, and encephalitis highlight the neurological impact of SARS-CoV-2. We employed a systems biology approach to analyze omics transcriptional data, exploring the molecular mechanisms underlying neurological complications in COVID-19. Methods: We retrieved post-mortem brain data of COVID-19 patients from the gene expression omnibus (GEO) dataset and constructed protein-protein interaction (PPI) networks for differentially expressed genes (DEGs) in the brain cortex and choroid plexus. Topologically crucial genes were identified, and MCODE clusters were analyzed for functional enrichment using the STRING database. Genes related to neurological symptoms (headache, seizure, stroke, meningitis, encephalitis) were extracted from the Comparative Toxicogenomics Database (CTD), and their associations with MCODE clusters were assessed via Fisher's exact test. Crucial gene interactions with FDA-approved drugs were also investigated. Results: We identified a cluster of heat shock protein (HSP) genes (HSP90AA1, HSPA1A, HSPA1B, HSPB1, HSPH1, HSPA5, DNAJB1, FKBP5) significantly correlated with all neurological manifestations. KEGG pathway enrichment showed associations with immune processes, neurodegenerative diseases (Parkinson's, Alzheimer's, Huntington's), virus-related pathways (Influenza A, Epstein-Barr, Measles), and pathways activated in viral infections. FKBP5, a key Hsp90 co-chaperone, interacts most with drugs that affect the nervous system in our drug-gene network. Conclusions: Shedding light on the molecular mechanisms behind COVID-19 neurological manifestations and possible drugs could pave the way for better managing future neurotrophic viruses. © 2025 Elsevier B.V., All rights reserved.