目的 采用分子对接技术筛选新型冠状病毒S蛋白与血管紧张素转化酶2（ACE2）小分子抑制剂。方法 化合物库采用Selleck中国天然产物库（目录号L1400，2 054种天然产物）。新型冠状病毒S蛋白与ACE2蛋白共晶采用周强研究员课题组发表结果（PDB：6M17）。采用Discovery Studio软件进行分子对接。结果 通过虚拟氨基酸突变实验确定了关键氨基酸，并在此基础上确定了结合空腔，进而从天然化合物库中筛选出11个具有潜在抑制新型冠状病毒S蛋白与ACE2作用的化合物：毛地黄皂苷、灰毡毛忍冬皂苷甲、连翘酯苷B、灰毡毛忍冬皂苷乙、川续断皂苷乙、常春藤苷D、桔梗皂苷D、松果菊苷、人参皂苷Rb₂、人参皂苷Rc、异绿原酸C。结论 从天然产物库中筛选出潜在的新型冠状病毒S蛋白-ACE2小分子抑制剂，为抗新型冠状病毒（SARS-CoV-2）药物研究及处方筛选提供参考。

Objective To screen inhibitors targeting SARS-CoV-2 S protein-ACE2 interaction by molecular docking. Methods Candidate natural products were collected from Selleck China natural product library (Catalog No. L1400, 2 054 natural products). The structure of SARS-CoV-2 S protein-ACE2 had been determined by Qiang Zhou team (PDB: 6M17). The molecular docking was performed by Discovery Studio. Results Based on the virtual amino acid mutation experiment which determined the key amino acids, the binding cavity was created. Then, 11 compounds were screened out from the natural compound library: digitonin, Lonicera grisea saponin A, forsythiaside B, L. grisea saponin B, Dipsacus asperges saponin B, hederacoside D, platycodon D, echinacoside, ginsenoside Rb₂, ginsenoside Rc, and chlorogenic acid C. Conclusion The 11 potential inhibitors targeting SARS-CoV-2 S protein-ACE2 interaction were screened out from natural products library, which provides a reference for the research of new anti SARS-CoV-2 drugs.

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国家自然科学基金资助项目（81700410）；四川省科技厅应用基础项目（2018JY0143）；四川省科技计划项目-重点研发项目（2019YFS0344）；西南民族大学中央高校基本科研业务费专项（2016NZYQN21）