An integrated bioinformatics approach reveals the potential role of microRNA-30b-5p and let-7a-5p during SARS CoV-2 spike-1 mediated neuroinflammation.

SARS-CoV-2 induced neuroinflammation contributing to neurological sequelae is one of the critical outcomes of long-COVID, however underlying regulatory mechanisms involved therein are poorly understood. We deciphered the profile of dysregulated microRNAs, their targets, associated pathways, protein-protein interactions (PPI), transcription factor-hub genes interaction networks, hub genes-microRNA co-regulatory networks in SARS-CoV-2 Spike-1 (S1) stimulated microglial cells along with candidate drug prediction using RNA-sequencing and multiple bioinformatics approaches. We identified 11 dysregulated microRNAs in the S1-stimulated microglial cells (p < 0.05). KEGG analysis revealed involvement of important neuroinflammatory pathways such as MAPK signalling, PI3K-AKT signalling, Ras signalling and axon guidance. PPI analysis further identified 11 hub genes involved in these pathways. Real time PCR validation confirmed a significant upregulation of microRNA-30b-5p and let-7a-5p; proinflammatory cytokines- IL-6, TNF-α, IL-1β, GM-CSF; and inflammatory genes- PIK3CA and AKT in the S1-stimulated microglial cells, while PTEN and SHIP1 expression was decreased as compared to the non-stimulated cells. Drug prediction analysis further indicated resveratrol, diclofenac and rapamycin as the potential drugs based on their degree of interaction with hub genes. Thus, targeting of these microRNAs and/or their intermediate signalling molecules would be a prospective immunotherapeutic approach in alleviating SARS-CoV-2-S1 mediated neuroinflammation; and needs further investigations.
Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.
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