湖北道地药材中潜在抗新型冠状病毒肺炎(COVID-19)活性成分的计算机虚拟筛选

Study on the virtual screening of potential active constituents against coronavirus disease 2019(COVID-19)of Dao-di herbs in Hubei Province

目的:运用计算机虚拟筛选技术寻找湖北道地药材中抗新型冠状病毒(SARS-CoV-2)的小分子抑制剂。方法:以药材名为关键词,在知网和PubMed数据库中搜索湖北道地药材的主要化学成分,从Pubchem数据库下载相应化合物结构,以新型冠状病毒3CL水解酶蛋白和血管紧张素转换酶Ⅱ(ACE2)为靶点,利用Sybyl软件中蛋白质预处理工具确定活性区域,应用Surflex-dock模块对小分子与靶蛋白进行分子对接,通过Total Score打分函数筛选出活性成分,采用Discovery Studio软件分析结合最好的蛋白复合体的相互作用力。结果:分子对接结果显示苍术苷A、厚朴木脂素C、异鼠李素是与SARS-CoV-23CL水解酶结合最强的3个化学成分,木兰苷B、3,4-O-二咖啡酰奎宁酸、木兰苷D是与ACE2结合最强的3个化学成分,与抑制剂洛匹那韦、利托那韦得分接近,可能为中药苍术、厚朴和菊花抗SARS-CoV-2的潜在活性成分,化合物与蛋白之间的相互作用力以氢键、疏水作用力为主。结论:基于分子对接技术虚拟筛选潜在的抗新型冠状病毒的中药化学成分,为湖北道地药材抗击SARS-CoV-2提供了科学指导与理论依据。

OBJECTIVE To search for small molecule inhibitors against novel coronavirus(SARS-CoV-2)in authentic medicinal materials in Hubei Province by computer virtual screening technique.METHODS The main chemical components of authentic medicinal materials in Hubei Province were searched in the CNKI and PubMed databases using the keywords of medicinal material name,the corresponding compound structures were downloaded from the Pubchem database,SARS-CoV-23 CL hydrolase protein and angiotensin-converting enzymeⅡ(ACE2)were used as targets,the active regions were determined using the protein preprocessing tool in Sybyl software,the molecular docking between small molecules and target proteins was performed using the Surflex-dock module,the active components were selected by the total score scoring function,and the interaction forces of the best protein complexes combined were analyzed using Discovery Studio software.RESULTS Atractyloside A,Magnolignan C andisorhamnetin are the three most effective components that bind to SARS-CoV-23 CL hydrolase,Magnoloside B and 3,4-dicaffeoylquinic acid and Magnoloside D are the three most effective components that bind to ACE2,and their scores were close to the inhibitors lopinavir and ritonavir.They may be potential active constituents of Atractylodis Rhizoma、Magnoliae Officinalis Cortex and Chrysanthemi Flos against SARS-CoV-2.The interaction forces were mainly hydrogen bonding and hydrophobic interaction.CONCLUSION The virtual screening of the potential chemical constituents of anti-novel coronavirus traditional Chinese medicine based on molecular docking technology provides scientific guidance and theoretical basis for the fight against SARS-CoV-2 using authentic herbs in Hubei Province.