Research on Active Compounds of Huanglian Jiedu Decoction for the Treatment of Corona Virus Disease 2019 Based on Network Pharmacology and Molecular Docking

Background: Huanglian Jiedu Decoction (HLJDD) is a traditional Chinese prescription for the treatment of influenza, inflammation and other ailments related to heat-syndrome, a typical pathological symptom in Traditional Chinese Medicine. It was recommended as one of the basic prescriptions among the Proposed Diagnoses and Treatment issued by China’s National Health Commission. In this work we investigated the molecular mechanism of action of Huanglian Jiedu Decoction in the treatment of Corona Virus Disease 2019 (COVID-19) through network pharmacology and molecular docking approaches. Methods: The chemical constituents and action targets of Coptis chinensis, Scutellaria baicalensis, Phellodendron amurense, Gardenia jasminoides in HLJDD were retrieved on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The database of UniProt and GeneCards were used to query the target genes that corresponding to the active compounds, and then a compound-target network was constructed using Cytoscape 3.7.2. GO database was used to annotate GO functions. Reactome was used to analyze KEGG enrichment pathway, predicting the possible mechanisms of active compounds. DAVID database was used to analysis the tissue enrichment. The main active ingredient is molecularly docked with the SARS-CoV-2, ACE2 and TMPRSS2. Results: We screened 84 compounds and obtained 341 corresponding target genes in the network. Gene annotation showed that the targets were involved mainly in 457 biological functions. 306 signaling pathways was enriched, involving chemokine and cytokine signaling pathways that mediate inflammation, interferon-γ signaling pathway, p53 pathway. And the targets mainly distributed in the lung liver and placenta, involving a variety of immune cells, such as T cells, B cells. The molecular docking results showed that core compounds such as beta-sitosterol, stigmasterol and quercetin had high affinity with SARS-CoV-2, ACE2 and TMPRSS2, which was comparable with drugs like abidol used to COVID-19 treatment by. Conclusions: The active compounds in HLJDD may have a therapeutic effect on COVID-19 through regulating multiple signal pathways by targeting genes such as VEGF, NOS2, IL6, MMP9, IL10, and TGFB1.