Decoding the mechanism of Qingjie formula in the prevention of COVID-19 based on network pharmacology and molecular docking.

Traditional Chinese medicine (TCM) has played a positive role in preventing and controlling the coronavirus disease 2019 (COVID-19) epidemic. Qingjie formula (QJF) developed to prevent COVID-19 is widely used in Wenzhou, Zhejiang province, China. However, the biological active ingredients of QJF and their specific mechanisms for preventing COVID-19 remain unclear. The study focused on exploring the pharmacological mechanism of QJF for the prevention of COVID-19 based on network pharmacology and molecular docking. The active ingredients of QJF were screened by TCMSP database. Databases such as Genecards and Swiss Target Prediction predicted potential targets of QJF against COVID-19. The "drug-active ingredient-potential target" network was constructed by Cytoscape software. We used STRING database to construct the protein-protein interaction (PPI) network. Enrichment of biological functions and signaling pathways were analyzed by using the DAVID database and R language. Then AutoDock Vina and Python software were used for molecular docking of hub targets and active ingredients. 147 active ingredients interacted with 316 potential targets of COVID-19. A PPI network consisting of 30 hub genes was constructed, and the top 10 hub genes were ALB, AKT1, TP53, TNF, IL6, VEGFA, IL1B, CASP3, JUN and STAT3. The results of GO analysis showed that these targets were mainly enriched in cell responses to oxidative stress, chemical stress, and other functions. KEGG analysis revealed that viral protein interactions with cytokines (e.g., human cytomegalovirus infection), endocrine resistance pathways (e.g., AGE-RAGE signaling pathway), PI3K-Akt signaling pathway, and lipid and atherosclerosis signaling pathway were the major signaling pathways. Moreover, the core active ingredients of QJF had good binding affinity with hub genes by molecular docking. QJF plays an important role in the prevention of COVID-19 by regulating host immune inflammatory response and oxidative stress response, inhibiting virus, improving immune function, regulating the hypoxia-cytokine storm, and inhibiting cell migration.