Network pharmacology and molecular docking analyses on Scutellaria barbata indicate that JUN and RELA are potential targets to treat and prevent COVID-19 viremia

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has been ongoing for more than two years and is likely to continue. Scutellaria barbata (S. barbata) is a traditional Chinese herbal medicine with anti-inflammatory and anti-viral properties and has demonstrated therapeutic effects on patients with COVID-19. Our study aims to shed light on the underlying mechanism and identify possible therapeutic targets. The data on the expression of COVID-19 viremia-associated genes were retrieved from five disease-gene databases. The expression pattern of genes encoding for functional monomer components of S. barbata was retrieved from the Traditional Chinese Medicine Systems Pharmacology platform. To determine the potential mechanism, we used “Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses,” and the protein-protein interaction (PPI) network was constructed using the STRING online tool. CytoNCA, a plug-in for Cytoscape, was used for screening the hub genes. The AutoDocktools and the “PyMOL” software were used for performing molecular docking between active molecules of drugs and disease-target proteins. We identified the S. barbata target and COVID-19 viremia-associated gene sets consisting of 42 genes. GO functional enrichment analysis showed that S. barbata can act by the regulation of cytokine activity and the cytokine-mediated signaling pathway. KEGG pathway enrichment analysis showed that these genes were enriched in several pathways like T helper cell 17 differentiation, the Tumor necrosis factor, and Interleukin-17 signaling pathways. In addition, we identified 17 hub genes, including JUN, RELA, TNF, IL6, etc., using the PPI network and subnetworks. Molecular docking was performed on two highly significant genes: JUN and RELA. The former is a transcription factor, regulating activation-induced cell death, Interferon response post-COVID-19 infection, CD95 ligand promoter activity, and the expression of cytokine genes in T-cells. The five active compounds of S. barbata, including baicalein, wogonin, quercetin, luteolin, and beta-sitosterol, could enter the active pockets of COVID-19 to exert potential therapeutic effects on COVID-19 viremia. JUN and RELA could weaken T cell-mediated immune and cytokine-related inflammatory responses. They could be used as therapeutic targets and could aid in reducing COVID-19 viremia.