目的 通过对清肺排毒汤功效和新型冠状病毒肺炎（COVID-19）病机的分析，基于计算机辅助药物设计（CADD）从多靶点结构出发系统探索清肺排毒汤排毒、抑制炎症风暴、利水渗湿3个方面的物质基础和分子机制。方法 TCMSP下载清肺排毒汤成分，基于血管紧张素转化酶II（ACE2）、白细胞介素-6受体（IL-6R）和水通道蛋白（AQP）分别进行分子对接虚拟筛选并对其结合模式进行分析。对利水药白术、茯苓、猪苓、泽泻进行反向靶点预测和GO分析和KEGG通路富集分析，预测其作用机制。结果 阻断病毒作用最突出的前3位中药为甘草、麻黄、枳实，抑制炎症作用最突出的前3位中药是甘草、柴胡、紫菀；清肺排毒汤4个子方中，小柴胡汤阻断病毒、抑制炎症风暴的潜在活性化合物数均排第1。槲皮素及其衍生物对ACE2和IL-6R 2个靶点均具有较强结合能力，是潜在的双靶点活性化合物。ACE2的Lys 353残基是化合物与ACE2结合的关键位点。白术、茯苓、猪苓、泽泻缺乏阻断病毒、抑制炎症风暴的化合物，分子对接结果显示，这4味药材中含有的东莨菪内酯、去氢齿孔酸、α-D-半乳糖、环氧泽泻烯具有与水通道蛋白4（AQP4）的潜在结合能力。结论 清肺排毒汤可通过多种化合物分别与ACE2、IL-6R、AQP4结合，发挥排毒、抑制炎症风暴、利水渗湿的作用；各组成子医方配伍合理，通过多点协同、优势互补发挥防治作用；得到了中药阻断新型冠状病毒（SARS-CoV-2）成分关键的结合位点Lys 353，为清肺排毒汤药效机制的多角度挖掘和单体成分的现代化开发提供线索。

Objective Based on the multi-target structure of computer aided drug design (CADD), the material basis and molecular mechanism of QPD were systematically discussed from three aspects of detoxification, anti-inflammatory storm and promoting urination and draining dampness, so as to analyze the efficacy of Qingfei Paidu Decoction (QPD) and the pathogenesis of COVID-19. Methods Compounds of QPD were downloaded from TCMSP, and molecular docking virtual screening was conducted based on angiotensin-converting enzyme II (ACE2), interleukin-6 receptor (IL-6R), and aquaporins (AQP), and their binding patterns were analyzed; Reverse target prediction, GO function enrichment analysis, and KEGG pathway enrichment analysis were carried out for Atractylodes macrocephala, Poria cocos, Polyporus umbellatus, Alisma orientale, and the mechanism of action was predicted. Results The most prominent drugs to block the virus were Glycyrrhiza uralensis, Ephadra sinica and Citrus aurantium; While the top three with inhibiting the inflammation effects were G. uralensis, Bupleurum chinense, and Asteris tataricus. Among the four sub-prescriptions of QPD, Xiaochaihu Decoction ranked first in the number of potentially active compounds to block virus and suppress inflammatory storm. Quercetin and its derivatives had high binding ability to ACE2 and IL-6R targets, which were potential dual-target active compounds. Lys 353 of ACE2 was the key site of ACE2 binding in Chinese medicine monomer compound. Atractylodes macrocephala, Poria cocos, Polyporus umbellatus and Alisma orientale lacked compounds that blocked viruses and suppressed inflammatory storms, but scopoletin, dehydroeburicoic acid, α-D-galactose, and alismoxide in these four herbs had potential binding ability with AQP4. Conclusion QPD can play the role of detoxification, suppression of inflammatory storm, and promoting urination and draining dampness in the treatment of COVID-19 by combining with ACE2, IL-6R and AQP4. Each component of the sub-medical prescription is reasonable compatibility, through multi-point cooperation, complementary advantages to play the role of prevention and cure; Blocking the key binding site of the virus, Lys 353, is known, which provides clues for the multi-angle exploration of the pharmacodynamic mechanism of QFPDT and the modern development of monomers.

R285.5

甘肃省新型冠状病毒肺炎（NCP）科技重大专项（2020）；2020年度甘肃中医药大学新型冠状病毒感染的肺炎应急防治专项项目（2020XGZX-01，2020XGZX-02）；甘肃省高等学校科研项目（2017A-048）；2020年度甘肃省重大疾病分子医学与中医药防治研究重点实验室新型冠状病毒防治研究专项开放基金资助项目（FZYX20-1，FZYX20-2，FZYX20-3）