TCMSP数据库中药化学成分的SARS-CoV-2主蛋白酶抑制剂虚拟筛选  

Virtual Screening of SARS-CoV-2 Mpro Protease Inhibitors Based on the Chemical Components of Traditional Chinese Medicine in TCMSP Database

作　　者：史海龙[1] 黄月 程怡 史永恒[1] 王川[1] 刘继平[1] 王斌[1] SHI Hailong;HUANG Yue;CHENG Yi;SHI Yongheng;WANG Chuan;LIU Jiping;WANG Bin(Shaanxi University of Chinese Medicine,Xixian New Area 712046 Shaanxi,China)

机构地区：[1]陕西中医药大学,陕西西咸新区712046

出　　处：《中药新药与临床药理》2022年第2期219-227,共9页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家留学基金委资金资助项目(201908610138);国家级大学生创新创业项目(201910716031);陕西省中医管理局中医药科研课题(JCMS003);陕西中医药大学创新团队项目(2019-YL13)。

摘　　要：目的运用计算机模拟技术从中药系统药理学数据库与分析平台(TCMSP)的中药化学成分中挖掘SARS-CoV-2主蛋白酶(Main protease,Mpro)抑制剂。方法运用类药性评估、分子对接、ADME预测、结合自由能计算、分子动力学模拟等多轮虚拟筛选的策略,从TCMSP数据库中筛选Mpro抑制剂。结果共筛选得到10个命中分子,其中前3位最佳命中分子为MOL003392、MOL011716、MOL002966,表现出与靶标活性口袋关键氨基酸残基的强相互作用。结论该研究可为发现SARS-CoV-2 Mpro小分子抑制剂提供新的思路。Objective Computer simulation technology was used to discover SARS-CoV-2 main protease(Mpro)inhibitors from chemical components of TCMSP database. Methods Multiple rounds of virtual screening strategies such as drug-like evaluation,molecular docking,ADME prediction,binding free energy calculation,molecular dynamics simulation,etc.,were conducted to screen Mpro inhibitors from the TCMSP database. Results Ten hits were obtained, among which the top 3 best hits MOL003392, MOL011716, and MOL002966 showed strong interactions with key amino acid residues in the target active pocket. Conclusion This study provides a new idea for the discovery of small molecules as SARS-CoV-2 Mpro inhibitors.

关 键 词：SARS-CoV-2 主蛋白酶(Mpro) 分子对接 虚拟筛选 分子动力学模拟 

分 类 号：R285.5[医药卫生—中药学] R857.3[医药卫生—中医学]