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目的 本研究通过网络药理学和分子对接技术预测黄连解毒汤(HLJDD)治疗新型冠状病毒肺炎(COVID-19)的潜在靶点和作用机制.方法 在中药系统药理学数据库和分析平台(TCMSP)、SymMap v2、中药百科全书(ETCM)、高通量中医药实验和参考指导数据库(HERB)、中医药综合数据库(TCMID)中检索HLJDD的化学成分和作用靶点.通过UniProt、GeneCards等数据库获取靶点对应的基因,运用Cytoscape 3.7.2构建化合物-靶点(基因)网络.通过基因本体(GO)数据库进行GO功能注释,运用GO和基因组百科全书(KEGG)预测活性化合物可能的作用机制.运用注释、可视化和集成发现数据库(DAVID)进行组织富集分析.将HLJDD的主要活性成分与其相应的相关靶点进行分子对接分析.结果 化合物-靶点网络包含76个化合物和458个相应靶点.基因注释显示预测的靶标主要参与了1953个生物过程;884条信号通路,包括白介素信号通路、免疫系统细胞因子信号通路、通用转录通路和RNA聚合酶II转录.药物潜在靶点主要分布在肺、肝和胎盘,涉及多种免疫细胞,如T细胞、B细胞.分子对接结果表明:汉黄芩素、小檗碱、黄芩素等核心化合物与肿瘤坏死因子(TNF)、胰岛素(INS)和肿瘤蛋白P53(TP53)具有高亲和力.结论 HLJDD中的活性化合物可能通过血管内皮生长因子A(VEGFA)、INS、白细胞介素6(IL-6)、TNF、半胱氨酸蛋白酶3、TP53和丝裂原活化蛋白激酶3(MAPK3)等靶向基因调节多条信号通路对COVID-19发挥治疗作用.“,”Objective To investigate and predict the molecular targets and mechanism of Huanglian Jiedu Decoction (黄连解毒汤,HLJDD) in the treatment of Corona Virus Disease 2019 (COV-ID-19) through network pharmacology and molecular docking analysis.Methods The chemical constituents and action targets of HLJDD were retrieved on Tradi-tional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SymMap v2, Encyclopedia of Traditional Chinese Medicine (ETCM), a High-throughput Ex-periment- and Reference-guided Database of Traditional Chinese Medicine (HERB), and Tra-ditional Chinese Medicine Integrated Database (TCMID). 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. Gene Ontology (GO) database was used to annotate GO functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to predict the possible mechanisms of active compounds. The Database for Annotation, Visu-alization and Integrated Discovery (DAVID) was used to analysis the tissue enrichment. The main active compounds in HLJDD are molecularly docked with their corresponding related targets. Results Seventy-six compounds were screened and 458 corresponding targets in the network were obtained. Gene annotation showed that the targets were involved mainly in 1953 biolo-gical processes. 884 signaling pathways was enriched, involving signaling by interleukins, cy-tokine signaling in immune system, generic transcription pathway, and RNA polymerase Ⅱ transcription. The targets mainly distributed in the lung, liver, and placenta, involving a vari-ety of immune cells, such as T cells and B cells. The molecular docking results showed that core compounds such as wogonin, berberine, and baicalein had high affinity with tumor nec-rosis factor (TNF), insulin (INS), and tumor protein 53 (TP53). Conclusion The active compounds in HLJDD may have a therapeutic effect on COVID-19 through regulating multiple signal pathways by targeting genes such as vascular endothelial growth factor A (VEGFA), INS, interleukin-6 (IL-6), TNF, caspase-3 , TP53, and mitogen-activ-ated protein kinase 3 (MAPK3).