Introduction: As the COVID-19 pandemic spreads worldwide, reports about the neurological complications of SARS-CoV-2 are excessively increasing. However, there is still insufficient high-throughput data on neuronal cells infected with SARS-CoV-2 to help predict its neural pathogenesis. HCoV-OC43 is another member of the beta coronavirus family that has confirmed neuro-invasive effects and has available neural omics data. This study predicts the critical genes, biological processes, and pathways mediating in SARS-CoV-2 neurological manifestations using a systems biology approach.Method: We retrieved raw data related to SARS-CoV-2 and HCoV-OC43 infections from gene expression omnibus datasets (GSE147507 and GSE13879 respectively). We constructed gene regulatory networks for both infections, detected significant regulatory motifs by FANMOD software, and created their subnetworks. We also constructed PPI networks and identified the MCODE clusters. In the intersection of merged subnetworks of two viruses, the most critical genes were verified in GRN & PPI networks. We drug-repurposed for the selected target genes and performed the functional enrichment analysis using DAVID and String databases.Results: Some of the top KEGG pathway results included NF-kappa B, Toll-like receptor, NOD-like receptor, MAPK, and Neurotrophin signaling pathways. The most essential identified genes included IL6, TNF, HOXA5, POU2F2, ITGB3, STAT1, YY1, E2F6, ESR1, FOXO3, FOXO1, MEF2A, ATF3, ATF4, DDIT3, TCF4, BCL2L2, and BMP4. These genes were also involved in mechanisms of other viral infections of the nervous system. This study repurposes nine medicines with effects on COVID-19 neurological complications. Some of the repurposed drugs were previously registered in clinical trials for COVID-19 treatment.Conclusion: We recommended some identified crucial genes and medications to investigate further their potential role in treating COVID-19 neurological complications.
The world has recently been plagued by a new coronavirus infection called SARS-CoV-2. This virus may lead to severe acute respiratory syndrome followed by multiple organ failure. SARS-CoV-2 has approximately 80–90% genetic similarity to SARS-CoV. Given the limited omics data available for host response to the viruses (more limited data for SARS-CoV-2), we attempted to unveil the crucial molecular mechanisms underlying the SARS-CoV-2 pathogenesis by comparing its regulatory network motifs with SARS-CoV. We also attempted to identify the non-shared crucial molecules and their functions to predict the specific mechanisms for each infection and the processes responsible for their different manifestations. Deciphering the crucial shared and non-shared mechanisms at the molecular level and signaling pathways underlying both diseases may help shed light on their pathogenesis and pave the way for other new drug repurposing against COVID-19. We constructed the GRNs for host response to SARS-CoV and SARS-CoV-2 pathogens (in vitro) and identified the significant 3-node regulatory motifs by analyzing them topologically and functionally. We attempted to identify the shared and non-shared regulatory elements and signaling pathways between their host responses. Interestingly, our findings indicated that NFKB1 , JUN , STAT1 , FOS , KLF4 , and EGR1 were the critical shared TFs between motif-related subnetworks in both SARS and COVID-1, which are considered genes with specific functions in the immune response. Enrichment analysis revealed that the NOD-like receptor signaling, TNF signaling, and influenza A pathway were among the first significant pathways shared between SARS and COVID-19 up-regulated DEGs networks, and the term “metabolic pathways” (hsa01100) among the down-regulated DEGs networks. WEE1, PMAIP1, and TSC22D2 were identified as the top three hubs specific to SARS. However, MYPN , SPRY4 , and APOL6 were the tops specific to COVID-19 in vitro. The term “Complement and coagulation cascades” pathway was identified as the first top non-shared pathway for COVID-19 and the MAPK signaling pathway for SARS. We used the identified crucial DEGs to construct a drug–gene interaction network to propose some drug candidates. Zinc chloride, Fostamatinib, Copper, Tirofiban, Tretinoin, and Levocarnitine were the six drugs with higher scores in our drug–gene network analysis. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-023-03518-x.
Mycobacterium bovis (M. bovis) is a slow-growing bacteria that can intracellularly reduce selenium ions to elemental selenium nanoparticles (SeNPs). We used bacterial lysates along with vitamin C to help the synthesis of SeNPs coated with M. bovis Bacille Calmette-Guérin (BCG) crude hydrophobic materials. However, the large-scale fabrication, separation, extraction, and purification of intercellular SeNPs which are prepared by using M. bovis, have many complexities. So, we developed a simple method for preparation of above BCG-coated nanoparticles and tested its potential immune-modulatory effects. In the current investigation, we cultivated the M. bovis in conventional media and prepared total cell lysates from this bacterium by just applying freeze and thaw and ultra-sonication. The resulting cell lysates were added to the solution containing selenium ions before adding the ascorbic acid as a reducing agent. At the end of the process, the fabricated selenium nanoparticles were separated by centrifugation and characterized by different instrumentation methods. In the next step, to evaluate the immune-modulatory effects of the hepatitis B surface antigen (HBsAg) vaccine alone, and in combination with plain SeNPs or SeNPs-BCG lysate, the serum level of interferon-gamma (IFN-γ) was determined in different groups by enzyme-linked immunosorbent assay (ELISA). This study showed adjuvant effects of prepared nanoparticles (in both 10 µg/300 µL and 100 µg/300 µL doses) in increasing the level of interferon-gamma (IFN-γ) in comparison with vaccine alone. Moreover, in both doses of SeNPs-BCG lysate, the level of interferon-gamma (IFN-γ) was remarkably higher than the same doses of plain SeNPs. As a result, synthesized SeNPs in the presence of whole-cell lysates of M. bovis indicated a greater ability to induce the interferon-gamma (IFN-γ) compared with other groups. Additionally, its easy fabrication procedure can be considered its superiority.
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