基于分子对接法和网络药理学揭示小柴胡汤防治新型冠状病毒肺炎的活性成分及作用机制

he present studyDiscovery of the action mechanisms and maStudy of the protective effects of Xiaochaihu Decoction on COVID-19 based on molecular docking and network pharmacology methodsjor bioactive compounds responsible for the protective effects of Xiaochaihu Decoction on COVID-19 aims to explore the mechanism of action and active constituents in Xiaochaihu Decoction (XCHD) for treatment of COVID-19, and provide a reference for its clinical application. The chemical constituents in XCHD were collected by using Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). Further molecular docking study was performed by using Discovery Studio to evaluate the interactions between these constituents and the ACE2, MPro, and PLP target proteins. The target proteins and genes of constituents were collected by using TCMSP and Toxicogenomics Database (CTD). Protein-protein interaction (PPI) data was constructed by using String website to screen key targets. The "herb-active constituent-key target" network was constructed by using Cytoscape software, followed by topology analysis. Moreover, KEGG pathway analysis were performed on screened key targets with the DAVID database to predict the mechanism of action of XCHD. Molecular docking results indicated that 86, 114, and 105 active constituents in XCHD possess higher Libdockscore (Libdockscore > 120) for binding to ACE2, MPro, and PLP, respectively. A total of 118 key targets were screened, such as PTGS2, AR, MAPK14, PPARG, GSK3B, CCNA2, MAPK1, MAPK3, TP53, IL6, CHEK1, JUN, STAT3, TNF, and RELA. Further KEGG pathway analysis revealed several key pathways which were probably involved in the treatment of COVID-19, including Influenza A pathway, Small cell lung cancer pathway, TNF signaling pathway, Toll-like receptor signaling pathway, PI3K-Akt signaling pathway, and HIF-1 signaling. In summary, XCHD exhibit therapeutic effects against COVID-19 probably by acting on ACE2, MPro, and PLP to inhibit the infection and reproduction of SARS-CoV-2. Meanwhile, XCHD may attenuate cytokine release syndrome and alleviate hypoxemia through multi-target and multi-pathway.