Network pharmacology and molecular docking-based investigations of Kochiae Fructus's active phytomolecules, molecular targets, and pathways in treating COVID-19.

ABSTRACT

COVID-19 disease is caused by SARS-CoV-2. Hyper-inflammation mediated by proinflammatory cytokines is humans' primary etiology of SARS-CoV-2 infection. Kochiae Fructus is widely used in China as traditional Chinese medicine (TCM) to treat inflammatory diseases. Due to its anti-inflammatory properties, we hypothesized that Kochiae Fructus would be a promising therapeutic agent for COVID-19. The active phytomolecules, targets, and molecular pathways of Kochiae Fructus in treating COVID-19 have not been explored yet. Network pharmacology analysis was performed to determine the active phytomolecules, molecular targets, and pathways of Kochiae Fructus. The phytomolecules in Kochiae Fructus were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and their potential targets were predicted with the SwissTargetPrediction webserver. COVID-19-related targets were recovered from the GeneCards database. Intersecting targets were determined with the VENNY tool. The Protein-protein interaction (PPI) and Molecular Complex Detection (MCODE) network analyses were constructed using the Cytoscape software. Using the DAVID tool, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the intersecting targets. AutoDock Vina (version 1.2.0.) was used for molecular docking analysis. Six active phytomolecules and 165 their potential targets, 1,745 COVID-19-related targets, and 34 intersecting targets were identified. Network analysis determined 13 anti-COVID-19 core targets and three key active phytomolecules (Oleanolic acid, 9E,12Z-octadecadienoic acid, and 11,14-eicosadienoic acid). Three key pathways (pathways in cancer, the TNF signaling pathway, and lipid and atherosclerosis) and the top six anti-COVID-19 core targets (IL-6, PPARG, MAPK3, PTGS2, ICAM1, and MAPK1) were determined to be involved in the treatment of COVID-19 with active phytomolecules of Kochiae Fructus. Molecular docking analysis revealed that three key active phytomolecules of Kochiae Fructus had a regulatory effect on the identified anti-COVID-19 core targets. Hence, these findings offer a foundation for developing anti-COVID-19 drugs based on phytomolecules of Kochiae Fructus.