Glycyrrhetinic acid: A potential drug for the treatment of COVID-19 cytokine storm

The cytokine storm (CS) triggered by coronavirus disease 2019 (COVID-19) has caused serious harm to health of humanity and huge economic burden to the world, and there is a lack of effective methods to treat this complication.In this research, we used network pharmacology and molecular docking to reveal the interaction mechanism in the glycyrrhetinic acid (GA) for the treatment of CS, and validated the effect of GA intervention CS by experiments.First, we screened corresponding target of GA and CS from online databases, and obtained the action target genes through the Venn diagram. Then, protein-protein interaction (PPI) network, Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the action target genes were acquired by R language to predict its mechanism. Next, molecular docking was performed on core targets. Finally, experiments in which GA intervened in lipopolysaccharide (LPS)-induced CS were implemented.84 action target genes were obtained from online database. The PPI network of target genes showed that TNF, IL6, MAPK3, PTGS2, ESR1 and PPARG were considered as the core genes. The results of GO and KEGG showed that action target genes were closely related to inflammatory and immune related signaling pathways, such as TNF signaling pathway, IL-17 signaling pathway, Human cytomegalovirus infection, PPAR signaling pathway and so on. Molecule docking results prompted that GA had fine affinity with IL6 and TNF proteins. Finally, in vivo and in vitro experimental results showed that GA could significantly inhibit LPS-induced CS.GA has a potential inhibitory effect on CS, which is worthy of further exploration.