摘要
以分子对接法探索中草药七叶一枝花治疗新型冠状病毒SARS-CoV-2的活性化合物。SARS-CoV-2主要通过其S蛋白与人体细胞表面的Angiotensin-converting enzyme 2(ACE2)受体结合。本研究通过分子对接模拟预测了七叶一枝花中富含的3种重楼皂苷(Ⅰ、Ⅵ、Ⅶ)与ACE2的结合亲和力。结果表明:三种重楼皂苷均能够与ACE2结合,结合自由能均低于-8 kcal/mol。三种化合物共同结合的氨基酸残基包括:Pro-346、Thr-347、Ala-348、Asp-350、Asn-394、His-401、Glu-402。三种药物结合以上位点的结构主要是共同的母核结构起着关键作用。另外,重楼皂苷Ⅰ与ACE2结合所需能量最低,而重楼皂苷Ⅵ与靶蛋白作用的关键氨基酸数量最多及形成的氢键数量最多。因此,基于这三种有效成分进行结构设计有望获得高效的SARS-CoV-2抑制剂,以期为COVID-19治疗药物发现提供研究基础。
To explore the active compounds of Chinese herbal medicine Paris polyphylla in the treatment of SARS-CoV-2.SARS-CoV-2 mainly binds to the angiotensin-converting enzyme 2(ACE2) receptor on the surface of human cells through its S protein.In this study,the molecular docking simulation method was used to predict the binding affinity of ACE2 and three kinds of polyphyllin(Ⅰ,Ⅵ,Ⅶ) rich in Paris polyphylla.The results show that the three polyphyllin can bind well with ACE2,and the binding free energy is lower than-8 kcal/mol.The amino acid residues combined by the three compounds include: Pro-346,Thr-347,Ala-348,Asp-350,Asn-394,His-401,Glu-402.The core structure shared by the three drugs plays a key role in binding the above sites.In addition,the energy required for the binding of polyphyllin Ⅰ to ACE2 is the lowest,while the number of key amino acids and the number of hydrogen bonds formed by the interaction of polyphyllin Ⅵ with the target protein are the largest.Therefore,structural design based on these three active ingredients is expected to obtain highly effective SARS-CoV-2 inhibitors,in order to provide a research basis for the discovery of COVID-19 therapeutic drugs.
作者
司渊
王纠
张亮
刘雪文
刘莹
SI Yuan;WANG Jiu;ZHANG Liang;LIU Xue-wen;LIU Ying(School of Basic Medical Sciences;Hubei Kep Laboratory of Embryonic Stem Cell Research;Hubei Key Laboratory of Wudang Local Chinese Medicine Research and Institute of Medicinal Chemistry;Biomedical Research Instinute,Hubei University of Medicine,Shiyan 442000,China)
出处
《天然产物研究与开发》
CAS
CSCD
北大核心
2020年第7期1099-1103,共5页
Natural Product Research and Development
基金
湖北省高等学校优秀中青年科技创新团队计划(T201915)
武当特色中药研究湖北省重点实验室开放课题(WDCM2019008)
湖北医药学院PI项目(HBMUPI201806)。
作者简介
通信作者:刘莹,Tel:86-015071577382,E-mail:ying_liu1002@163.com。
