基于分子对接方法进行金银花、连翘抗流感病毒H7N9的研究

Molecular Docking- based Study on the Anti- influenza H7N9 of Flos Lonicerae and Fructus Forsythiae

目的从金银花-连翘药对中寻找能够应对流感病毒H7N9的潜在抑制剂。方法以H7N9神经氨酸酶N9及其两种突变型N9-R294K和N9-R292K为受体,以金银花-连翘中24个化合物为配体,应用分子对接方法研究配体与受体之间的相互作用关系。结果研究发现金银花-连翘药对中19个成分与H7N9神经氨酸酶发生作用。其中M1、M4、M5、M7、M8、M10、M12、M14、M16、M17、M19、M22、M23等小分子是金银花-连翘药对作用H7N9神经氨酸酶的主要化合物。分子对接结果显示M4和M22与N9、N9-R294K、N9-R292K的对接分值分别为9.86、11.42、8.02、8.69、11.15、7.24;M5、M10与N9-R294K对接得分为10.36、8.36,均显著高于对照组奥司他韦羧酸盐。结论金银花-连翘药对能够通过分子间的协同效应有效防治H7N9流感病毒。M4(连翘酯苷A)和M22(亚油酸乙酯)可以作为流感病毒H7N9(包括两种突变型)的潜在抑制剂进行进一步研究开发。

Objective： The purpose of this paper is to find the potential inhibitors of influenza H7N9 from herbal medicine Flos Lonicerae and Fructus Forsythiae. Methods： In this study,we used the general H7N9 neuraminidase（ N9）and oseltamivir- resistant neuraminidase including N9- R294 K and N9- R292 K mutations as acceptors and employed the 24 small molecules in Flos Lonicerae and Fructus Forsythiae as ligands to perform the molecular docking for exploring the binding abilities between these small molecules and neuraminidase. Results： According to the docking scores（ =6）,we found the 19 components in the herbs showed obvious synergistic effect to fight influenza H7N9. Comparing the docking results with oseltamivir. M1,M4,M5,M7,M8,M10,M12,M14,M16,M17,M19,M22,M23 showed high scores which could be as the main composition of Flos Lonicerae and Fructus Forsythiae to inhibit H7N9. Among these molecules,M4,M5,M10,M22 present oseltamivir- comparable high scores with neuraminidase,but M4 and M22showed interaction with 3 different subtypes of N9. Conclusion： Flos Lonicerae and Fructus Forsythiae can inhibit H7N9 neuraminidase including drug- resistant mutants through synergistic effect and the small molecules M4（ Forsythoside A）and M22（ Ethyl linoleate） can be as potential inhibitors for neuraminidase of H7N9.