Exploring common pathogenic association between [EBV] and [LC] by integrating RNA-Seq and molecular dynamics simulations, 2024, Kanwal+Zhang

Discussion in 'Long Covid research' started by SNT Gatchaman, Oct 13, 2024.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

    Messages:
    5,923
    Location:
    Aotearoa New Zealand
    Exploring common pathogenic association between Epstein Barr virus infection and long-COVID by integrating RNA-Seq and molecular dynamics simulations
    Kanwal, Ayesha; Zhang, Zhiyong

    The term "Long-COVID" (LC) is characterized by the aftereffects of COVID-19 infection. Various studies have suggested that Epstein–Barr virus (EBV) reactivation is among the significant reported causes of LC. However, there is a lack of in-depth research that could largely explore the pathogenic mechanism and pinpoint the key genes in the EBV and LC context. This study mainly aimed to predict the potential disease-associated common genes between EBV reactivation and LC condition using next-generation sequencing (NGS) data and reported naturally occurring biomolecules as inhibitors.

    We applied the bulk RNA-Seq from LC and EBV-infected peripheral blood mononuclear cells (PBMCs), identified the differentially expressed genes (DEGs) and the Protein–Protein interaction (PPI) network using the STRING database, identified hub genes using the cytoscape plugins CytoHubba and MCODE, and performed enrichment analysis using ClueGO. The interaction analysis of a hub gene was performed against naturally occurring bioflavonoid molecules using molecular docking and the molecular dynamics (MD) simulation method.

    Out of 357 common genes, 22 genes (CCL2, CCL20, CDCA2, CEP55, CHI3L1, CKAP2L, DEPDC1, DIAPH3, DLGAP5, E2F8, FGF1, NEK2, PBK, TOP2A, CCL3, CXCL8, DEPDC1, IL6, RETN, MMP2, LCN2, and OLR1) were classified as hub genes, and the remaining ones were classified as neighboring genes. Enrichment analysis showed the role of hub genes in various pathways such as immune-signaling pathways, including JAK-STAT signaling, interleukin signaling, protein kinase signaling, and toll-like receptor pathways associated with the symptoms reported in the LC condition. ZNF and MYBL TF-family were predicted as abundant TFs controlling hub genes' transcriptional machinery. Furthermore, OLR1 (PDB: 7XMP) showed stable interactions with the five shortlisted refined naturally occurring bioflavonoids, i.e., apigenin, amentoflavone, ilexgenin A, myricetin, and orientin compounds. The total binding energy pattern was observed, with amentoflavone being the top docked molecule (with a binding affinity of –8.3 kcal/mol) with the lowest total binding energy of −18.48 kcal/mol.

    In conclusion, our research has predicted the hub genes, their molecular pathways, and the potential inhibitors between EBV and LC potential pathogenic association. The in vivo or in vitro experimental methods could be utilized to functionally validate our findings, which would be helpful to cure LC or to prevent EBV reactivation.


    Link | PDF (Frontiers in Immunology) [Open Access]
     
  2. Hutan

    Hutan Moderator Staff Member

    Messages:
    29,700
    Location:
    Aotearoa New Zealand
    33. Gold JE, Okyay RA, Licht WE, Hurley DJ. Investigation of long COVID prevalence and its relationship to epstein-barr virus reactivation. Pathogens. (2021) 10:763. doi: 10.3390/PATHOGENS10060763
    PubMed Abstract | Crossref Full Text | Google Scholar
    Forum thread: Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation, 2021, Gold et al
    Looks like I missed this 2021 paper.
    My impression had been that there wasn't a lot of proof to support the idea of EBV reactivation coinciding with PEM or bad ME/CFS days generally, and that there was some proof that EBV virus levels do not differ between ME/CFS/LC and healthy controls. But, I haven't read this paper.

    34. Paganelli R. Resurrecting epstein-barr virus. Pathogens. (2022) 11:772. doi: 10.3390/PATHOGENS11070772
    PubMed Abstract | Crossref Full Text | Google Scholar
     
    forestglip, Peter Trewhitt and shak8 like this.

Share This Page