传统中药中H7N9病毒神经氨酸酶抑制剂的计算机虚拟筛选

Virtual Screening of Potential H7N9 Virus Neuraminidase Inhibitors Based on Traditional Chinese Medicine Database

目的:运用计算机虚拟筛选技术从传统中药数据库(TCM database@Taiwan)中快速搜索H7N9亚型流感病毒神经氨酸酶(neuraminidase,NA)的中药小分子抑制剂。方法:采用Auto Dock Vina软件对蛋白质晶体结构数据库PDB中NA与小分子抑制剂扎那米韦形成的复合物(PDB代码为4MWX)三维结构活性部位进行分析,基于传统中药配体库进行分子对接初次筛选。综合运用传统中药系统药理学数据库及分析平台TCMSP及Accelrys公司开发的Discovery Studio 2.5分子模拟软件包内TOPKAT模块计算药代动力学参数和毒性预测对分子对接结果进行2次筛选。结果:以原配体(扎那米韦)的自由结合能为阈值,筛选出中国传统中药数据库中3个类药性良好的化学成分与NA亲和力高于上市的抗流感药物扎那米韦的天然小分子化合物,并且确定了它们的中草药来源。结论:该研究结果可促进从传统中药库中提取、设计及实验合成新抗H7N9流感病毒药物。

Objective： To take technology of computer virtual screening for fast searching small molecule inhibitors for H7N9 subtype of influenza virus neuraminidase（ NA） from traditional Chinese medicine database@Taiwan（ TCM database@Taiwan）. Method： Based on optimized complex structure of NA bound with specific inhibitor of Zanamivir,computer-aided structure-based virtual screening against TCMD database@taiwan was conducted to determine occurrence of herb-based NA inbitors in Auto Dock Vina software package of Scripps institution. Virtual screening results were further filtered by predictive ADME simulation by traditional Chinese medicine systems pharmacology database and analysis platform（ TCMSP） and simultaneously filtered by predictive toxic simulation using TOPKAT module from Discovery Studio 2. 5 software package. Result： Free binding energy of original ligand（ Zanamivir） could be used as a threshold,then not only obtained three compounds having a higher binding affinity than Zanamivir,but also they had good drug-likeness. Their sources of traditonal Chinese medicine had been determined. Conclusion： This study provides an important reference and a theoretical basis for extraction of antiviral compounds from Chinese herbal medicine and design of anti-influenza drugs.