目的 研究小柴胡汤在治疗新型冠状病毒肺炎（COVID-19）邪热郁肺、枢机不利证过程中的功效作用网络及潜在机制，分析方剂中抗新型冠状病毒（SARS-CoV-2）的活性成分。方法 首先查阅文献分析COVID-19邪热郁肺、枢机不利证与小柴胡汤适应证的方证对应关系，继而运用网络药理学技术Cytoscape 3.6.0等软件分别构建小柴胡汤“中药方剂-活性成分-关键靶点”功效作用网络，并确认方中抗SARS-CoV-2活性成分，从多方面分析小柴胡汤治疗早期COVID-19邪热郁肺、枢机不利证的功效作用及机制。结果 已有文献报道中药潜在抗SARS-CoV-2活性成分48个；共分析出小柴胡汤中治疗肺炎、调节免疫的活性成分140个，其中黄芩素、芒柄花素、槲皮素等12个成分具有潜在抗SARS-CoV-2活性。小柴胡汤中活性成分通过IL-6、NOS2、ESR1等95个关键靶点进行肺炎治疗和免疫调节，涉及TNF信号通路、IL-17信号通路、甲型流感等多条通路。基因共表达和蛋白-蛋白互相作用（PPI）分析发现，血管紧张素转化酶II（ACE2）仅与上述靶点中NOS2具有共表达，并且在PPI互作网络中也仅与5个靶点有相互作用关系，推测ACE2靶点仅在SARS-CoV-2入侵人体的时候起到重要作用，而在病毒感染后的肺炎治疗中作用甚微。结论 小柴胡汤中活性成分在抑制SARS-CoV-2活性、阻断SARS-CoV-2入侵途径、抑制炎症风暴、调节机体免疫等多方面发挥治疗COVID-19的作用；值得注意的是针对ACE2靶点设计药物可阻断病毒入侵，但对肺泡内炎症等病变疗效可能不佳，因此，这也为小柴胡汤对早期COVID-19治疗提供了多靶点、多向性空间。另外，小柴胡汤用于治疗早期COVID-19时尤应注意精准辨证用药，一是避免产生不良反应，二是避免加重COVID-19病情出现细胞因子损伤。
Objective To study the efficacy network and potential mechanism of Xiaochaihu Decoction (XCHD) in the treatment of coronavirus disease 2019 (COVID-19) with syndrome of pathogenic heat lingering in the lung and obstructive cardinalat, and analyze the active ingredients of XCHD with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficacy. Methods The correspondence between COVID-19 and XCHD was analyzed by literature consulting. Based on network pharmacology, Cytoscape 3.6.0 and other software were then used to construct XCHD efficacy network of "Chinese medicine prescription-active ingredient-key target" for pneumonia and immune regulation, in order to confirm anti-SARS-CoV-2 active ingredients in the prescription. Some softwares were used to analyze XCHD for COVID-19 treatment in multiple aspects. Results A total of 48 active ingredients with potential anti-SARS-CoV-2 effect in herbs were collected; 140 active ingredients in XCHD for pneumonia treatment and immune regulation were analyzed, of which 12 ingredients had direct anti-SARS-CoV-2 activity including baicalein, formononetin, quercetin, etc. The active ingredients in XCHD exerted efficacy for pneumonia treatment and immunoregulation through 95 key targets such as IL-6, NOS2, and ESR1, involving multiple pathways such as the TNF signaling pathway, IL-17 signaling pathway, and influenza A. Analysis of gene co-expression and PPI interaction analysis found that ACE2 only co-expressed with NOS2 in the above targets, and also interacted with only five targets in the PPI interaction network. It is speculated that the ACE2 target only plays an important role when SARS-CoV-2 invaded the human body, and had little effect in the treatment of pneumonia after viral infection. Conclusion The active ingredients in XCHD play a role in treating COVID-19 by inhibiting SARS-CoV-2 activity, blocking the SARS-CoV-2 invasion pathway, inhibiting cytokine storm, and regulating immunity. It is worth noting that drugs designed for the ACE2 target can block virus invasion, but may not be effective for diseases such as alveolar inflammation, Therefore, this study also provides a multi-target and multi-directional space for XCHD for early COVID-19 treatment. In addition, when XCHD is used in the early treatment of COVID-19, we should pay attention to the precise use of drugs based on syndrome accurate identification, one is to avoid adverse reactions, the other is to avoid cytokine damage caused by re-crown disease.