Decoding Shared Molecular Mechanisms of Sars-Cov-2 and Hcov-Oc43 in Covid-19 Neurological Manifestations: A Systems Biology Approach Publisher



M Mozafar MARYAM ; Sa Mirmotalebisohi Seyed AMIR ; M Sameni MARZIEH ; Z Dehghan ZEINAB ; H Zohrevand HASSAN ; Z Sepehrizadeh ZARGHAM ; Ma Faramarzi Mohammad ALI ; Ar Shahverdi Ahmad REZA ; H Zali HAKIMEH
Source: Gene Reports Published:2025

Abstract

Background and objectives: As the COVID-19 pandemic developed throughout the world, there were an excessive number of reports of SARS-CoV-2's neurological manifestations. This study investigated shared molecular mechanisms between SARS-CoV-2 and HCoV-OC43, considering their similar neuroinvasive effects and partial phylogenetic proximity. We aimed to enhance understanding of COVID-19 neural manifestations through a systems biology approach, decoding crucial genes, biological processes, and pathways to mediate SARS-CoV-2 neurological complications. Methods: We utilized high-throughput omics datasets from the Gene Expression Omnibus (GSE174745 for SARS-CoV-2 and GSE13879 for HCoV-OC43). We generated protein-protein interaction networks and MCODE clusters in Cytoscape. Significant relationships between the two infections were identified using the Fisher exact test, and the critical shared genes were selected as targets for drug repurposing. Real-time PCR assessed the expression levels of some crucial genes, and DAVID and STRING databases were used for functional enrichment studies. Results: Some shared enriched pathways mediating the COVID-19 pathogenesis included neurodegeneration, mTOR signaling, TNF signaling, complement and coagulation cascades, and Apoptosis. Our study confirmed changes in the expression levels of STAT1, YY1, ATF3, ATF4, and DDIT3 in neuro-COVID patients, with these genes previously implicated in other viral nervous system diseases. Among repurposed drugs with validated efficacy for respiratory complications of COVID-19, Estradiol valerate, Progesterone, Liothyronine, Spironolactone, Indomethacin, Aspirin, and Cyclosporine show potential therapeutic value for managing COVID-19's neurological effects. Conclusion: This validated systems biology study, supported by gene expression analysis, unveils molecular mechanisms and interactions crucial for understanding the neurological aspects of COVID-19. These findings lay the groundwork for future research and potential therapeutic strategies. © 2025 Elsevier B.V., All rights reserved.