基于分子对接筛选宣肺败毒方和血必净注射液中抑制新型冠状病毒RNA依赖的RNA聚合酶的活性物质

Screening bioactive compounds in the Xuanfei Baidu prescription and the Xuebijing injection for inhibiting SARS-CoV-2 RdRp based on molecular docking

目的:筛选宣肺败毒方和血必净注射液中抑制新型冠状病毒RNA依赖的RNA聚合酶(RNA Dependent RNA Polymerase,RdRp)的活性物质。方法:以新型冠状病毒RdRp作为分子对接的靶蛋白,使用AutoDockTools软件对其去水加氢。利用中药系统药理学数据库与分析平台(TCMSP)检索出宣肺败毒方和血必净注射液中的有效活性小分子化合物,将其导入Chem 3D中进行能量最小化,用AutoDockTools加氢、调节化学键,然后与处理后的RdRp在AutoDock Vina中进行分子对接。最后通过Pymol、Discovery Studio、Ligplot进行可视化处理。结果:从TCMSP中分别检索出宣肺败毒方活性成分230个、血必净注射液活性成分125个。通过分子对接技术筛选出19个与RdRp结合能低于-8.0 kcal/mol的化合物。经可视化处理发现,宣肺败毒方中的大黄素甲醚二葡萄糖苷和埃沃生物苷、血必净注射液中的丹参酚酸j可很好地作用于RdRp的活性口袋,且与RdRp形成传统氢键、碳氢键及疏水键等相互作用。结论:本研究从宣肺败毒方和血必净注射液中筛选出与核苷酸竞争性结合新型冠状病毒RdRp的小分子,为研发抗新型冠状病毒感染的特效药提供理论依据。

Objective:To screen the bioactive compounds in the Xuanfei Baidu prescription(宣肺败毒方)and the Xuebijing injection(血必净注射液)that inhibit SARS-CoV-2 RNA dependent RNA polymerase(RdRp).Methods:SARS-CoV-2 RdRp,dehydrated and hydrogenated by AutoDockTools,was used as the target protein for molecular docking.The effective active small molecule compounds in the Xuanfei Baidu prescription and the Xuebijing injection were retrieved by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and were then imported into Chem 3D for energy minimization.After hydrogenating and regulating chemical bond using AutoDockTools,the small molecule compounds were docked with the pretreated RdRp in AutoDock Vina.Finally,Pymol,Discovery Studio and Ligplot were used for visualization.Results:A total of 230 and 125 effective active components were retrieved from the Xuanfei Baidu prescription and the Xuebijing injection using TCMSP,respectively.Among them,19 compounds with binding energy lower than-8.0 kcal/mol were initially screened by molecular docking.Furthermore,the result of visualization showed that physciondiglucoside and evobioside in the Xuanfei Baidu prescription and the salvianolic acid j in the Xuebijing injection could act well on the active pocket of RdRp,and could interact with RdRp by forming traditional hydrogen bonds,carbonhydrogen bonds and hydrophobic bonds.Conclusion:In the study,several small molecules that competitively bind SARS-CoV-2 RdRp with nucleotides were screened from the Xuanfei Baidu prescription and the Xuebijing injection.The study provides a theoretical basis for the development of specific drugs against SARS-CoV-2.