流感病毒神经氨酸酶抑制剂的理性筛选

Rational drug screening on neuramidinase inhibitors of influenza virus

介绍了理性筛选流感病毒神经氨酸酶抑制剂的全过程,共分4个阶段:1)化合物数据库类药性处理;2)建立神经氨酸酶抑制剂三维药效团并对目标数据库进行构象搜索;3)分子对接及对接后分析;4)神经氨酸酶抑制模型的建立及待测化合物的活性检测。活性检测后发现4个活性化合物,其中IC_(50)为10^(-5)M 的化合物1个,IC_(50)为10^(-6)M的化合物2个,IC_(50)为10^(-7)M 的化合物1个。应用理性筛选方法,从化合物数据库中挑选出部分化合物进行神经氨酸酶抑制活性的筛选,减少了药物筛选的盲目性,提高了药物发现的机率。

In the process of the rational screening on neuramidinase(NA)inhibitors of influenza virus,there were 4 stages:1)Prepared for drug-like compound database;2)Established 3D pharmacophore model of NA inhibitors and searched con-formations in the target compound database;3)Selected the compounds by the result of molecular docking and did post-docking analysis.4)Established the assay model of NA inhibitor and assayed the compounds selected.In the and,wefound 4 activity compounds by applying the rational screening method.There were one compound with IC_(50) 10^(-5)M,twocompounds with IC_(50) 10^(-6)M and one compound with IC_(50) 10^(-7) M.In this way,only a small part of compounds selected fromthe database are assayed,so rational screening can increase the quality of screening compounds,decrease the waste of thecompound resource and increase the probability of drug discovery.