目的 基于中药系统药理学数据库和分析平台TCMSP，运用计算机虚拟筛选技术寻找新型冠状病毒（SARS-CoV-2）3CL水解酶的中药小分子抑制剂，推测潜在抗新型冠状病毒肺炎（COVID-19）中药及中药复方。方法 以SARS-CoV-2 3CL水解酶蛋白为靶点，利用Autodock Vina软件和Python脚本实现高通量分子对接，结合"ADME-Lipinski"规则进行再次筛选，以优选活性成分，推测关键中药及复方。基于网络药理学角度，构建成分-靶点-通路网络，推测核心药对的作用机制。结果 以SARS-CoV-2原配体为阳性对照，筛选出66个药动学性质良好的天然小分子抑制剂，优选出12味中药单味药，2个中药药对甘草-桑白皮和金银花-连翘，以及桑菊饮、桑菊饮合银翘散加减等12个中药处方作为抗SARS-CoV-2的候选方案。结论 基于高通量分子对接技术虚拟筛选SARS-CoV-2 3CL水解酶的中药小分子抑制剂及中药，结合网络药理学分析潜在分子机制，为中药抗击SARS-CoV-2提供了科学指导与理论依据。

Objective Based on the systematic pharmacological database of traditional Chinese medicine (TCM) and the analysis platform TCMSP, the computer virtual screening technique was used to screen the small molecule inhibitors of SARS-CoV-2 3CL hydrolase from Chinese materia medica (CMM), and speculate the potential anti-COVID-19 novel coronavirus pneumonia TCMs and its compounds. Methods SARS-CoV-2 3CL hydrolase protein was targeted in this study. Autodock Vina software and Python script were used to realize high-throughput molecular docking. Combined with "ADME-Lipinski" rules, the re-screening was carried out to optimize the active ingredients and speculate the key TCMs and compound prescriptions. Based on the perspective of network pharmacology, a component-target-pathway network was constructed to infer the mechanism of action of core drug pairs. Results Taking the reference ligand as positive control, 66 natural micromolecule compounds with good pharmacokinetic properties were obtained. Twelve single TCMs, two Chinese medicine pairs of Glycyrrhizae Radix et Rhizoma-Mori Cortex and Lonicerae Japonicae Flos-Forsythiae Fructus, and 12 TCM prescriptions including Sangju Drink and modified Sangju Drink and Yinqiao Powder were selected as candidate schemes to fight against novel coronavirus pneumonia. Conclusion This study is based on high-throughput molecular docking technology to virtually screen small molecule inhibitors of SARS-CoV-2 3CL hydrolase of CMM and Chinese medicines, innovatively analyze the potential molecular mechanism in combination with network pharmacology, and provide scientific guidance and theoretical basis for TCM to resist novel coronavirus pneumonia.

R285.5

国家自然科学基金资助项目（81873220）；国家自然科学基金资助项目（81774167）；山东省重点研发计划（2018CXGC1307）