基于计算机模拟技术以埃博拉病毒跨膜糖蛋白为靶点挖掘中药抗病毒活性分子

目的基于埃博拉病毒跨膜糖蛋白(transmembrane glycoprotein of the Ebola virus,EBOV-GP)的三维空间结构,运用计算机虚拟筛选技术从中国台湾中医药数据库TCM@TAIWAN中寻找具有抗病毒作用的中药活性分子。方法以EBOV-GP为靶点,采用类药性评估、分子对接、分子动力学模拟以及吸收、分布、代谢和排泄(absorption、distribution、metabolism and excretion,ADME)预测等多尺度虚拟筛选策略,从TCM@TAIWAN数据库中挖掘候选药效分子,并分析候选分子与靶点的相互作用情况。结果以胺碘酮为阳性对照药物,筛选出4个类药性良好的中药单体ZINC85531496、ZINC85567560、ZINC85592968、ZINC33833122,与EBOV-GP亲和力及相互作用基团均优于胺碘酮。结论采用多种计算机虚拟筛选技术挖掘EBOV-GP抑制剂,可促进从天然产物化学结构数据库中提取、设计以及实验合成抗埃博拉病毒的药效分子。

Mining antiviral active inhibitors in traditional Chinese medicine targeted with transmembrane glycoprotein of Ebola virus by in silico discovery

Objective Using computer virtual screening technology, some inhibitors of transmembrane glycoprotein of Ebola virus (EBOV-GP) would be sorted from TCM@TAIWAN Database. Methods Taking EBOV-GP as the target, using multi-scale virtual screening strategies such as drug-like evaluation, molecular docking, ADME prediction, molecular dynamics simulation, etc., the candidates were mined from TCM@TAIWAN database, and then the interaction between candidates and targets was analyzed. Results Amiodarone was used as a positive control, and four monomers (ZINC85531496, ZINC85567560, ZINC85592968 and ZINC33833122) from Chinese medicine with good drug-like properties were selected, and their affinity and interaction with EBOV-GP were superior to amiodarone. Conclusion A variety of computer virtual screening technologies to mine EBOV-GP inhib are used to facilitate the extraction, design, and experimental synthesis of anti-Ebola virus inhibitors from natural products chemical structure database.