目的 預測柴胡桂枝干姜湯干預初期寒濕郁肺型新型冠狀病毒肺炎（COVID-19）的藥效成分及關鍵靶標，明確其作用機制。方法 查閱文獻及臨床報道，總結COVID-19中醫(yī)分期、臨床表現(xiàn)及柴胡桂枝干姜湯的功用進行方證關系分析。運用TCMSP數(shù)據(jù)庫篩選柴胡桂枝干姜湯中潛在活性成分及相關靶點，PubMed等數(shù)據(jù)庫篩選肺炎、咳嗽、發(fā)熱相關靶點，借助Cytoscape軟件構建“藥物-疾病-靶點”的可視化網絡圖、蛋白互作網絡，并通過STRING數(shù)據(jù)庫進行關鍵靶點的GO和通路（pathway）富集分析，藥效成分采用AutoDock與新型冠狀病毒（SARS-CoV-2）3CL水解酶蛋白及血管緊張素轉化酶II（ACE2）進行分子對接。結果 方證關系分析柴胡桂枝干姜湯可奏溫陽散寒化濕、兼清郁熱、開達膜原之功干預初期寒濕郁肺型COVID-19，通過篩選，預測柴胡桂枝干姜湯中發(fā)揮治療作用主要為156個化學成分作用于159個相關靶點，核心基因有EGFR、TP53、YWHAZ、HSP90AB1、PIK3R1、GRB2等27個，GO和pathway分析柴胡桂枝干姜湯主要參與細胞調節(jié)等生物過程及免疫系統(tǒng)相關通路發(fā)揮治療作用，對10個核心成分進行分子對接所得，方中柴胡中柴胡皂苷A、柴胡皂苷D與桂枝中的過氧麥角固醇與SARS-CoV-2 3CL水解酶蛋白和ACE2有較好的親和力。結論 通過網絡藥理學與分子對接技術預測柴胡桂枝干姜湯可用于初期寒濕郁肺型COVID-19治療，方中柴胡、桂枝等中藥含有的潛在抗病毒成分可通過調控免疫系統(tǒng)等發(fā)揮治療作用，闡釋了中藥“多成分-多靶點-多疾病”的作用特點，為臨床用藥提供理論依據(jù)。

Objective To predict the efficacy components and key targets of Chaihu Guizhi Ganjiang Decoction (CGGD) in the intervention of novel coronavirus pneumonia in the cold-dampness obstructing lungs in early stage, and clarify its mechanism. Methods The novel coronavirus pneumonia TCM stage, clinical manifestations and the function of CGGD were analyzed by literature mining and clinical reports. TCMSP database was used to screen potential active components and related targets in CGGD. PubMed database was used to screen pneumonia, cough and fever related targets. With the help of Cytoscape software, a "drug-disease-target" visual network diagram and protein interaction network were constructed, and GO and pathway enrichment analysis of key targets was performed through the STRING database. The active ingredients were molecularly docked with SARS-CoV-2 3CL hydrolase protein and ACE2 by AutoDock Vina. Results The analysis of the relationship between prescriptions and syndromes showed that CGGD could play warm-yang scattered cold, resolve dampness, clear stagnation and heat, and open up membrane's power to intervene in early cold-dampness lung type COVID-19. Through screening, the therapeutic effects of CGGD were mainly in 156 chemical components acting on 159 related targets. The core 27 genes predicted and analyzed included EGFR, TP53, YWHAZ, HSP90AB1, PIK3R1, GRB2, etc. GO and pathway analysis showed that CGGD was mainly involved in biological processes such as cell regulation and immune system related pathways to play a therapeutic role. The 10 core components were molecularly docked, saikosaponin A, saikosaponin D, and peroxyergosterol in CGGD had good affinity with 3CL hydrolase protein and ACE2. Conclusion Using network pharmacology and molecular docking technology to predict that CGGD can be used for the treatment of novel coronavirus pneumonia with symptom of cold-dampness obstructing lungs in early stage, potential antiviral ingredients contained in prescription of CGGD, can play a therapeutic role in the treatment of new type of coronavirus pneumonia in the early stage by regulating the immune system. It explains the characteristics of "multi-component-multi-target-multi-disease" of Chinese materia medica, and provides theoretical basis for clinical rational use of medicines.

R285.5

山東省重點研發(fā)計劃（重大關鍵技術）項目（2017CXGC1301）；山東省重點研發(fā)計劃（重大關鍵技術）項目（2016ZDJS07A21）；泰山學者工程專項經費項目（ts201511107）