[基于细胞的2009 H1N1流感神经氨酸酶抑制剂评价体系的建立]

[Establishment of a cell-based 2009 H1N1 influenza neuraminidase inhibitors evaluation system].

作者信息

Zhang Chao, Cao Ying-li, Zhong Wu, Xiao Jun-hai, Guo Ying

机构信息

Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

出版信息

Yao Xue Xue Bao. 2010 Mar;45(3):383-7.

PMID:21351517

Abstract

This study is to establish a cell-based model targeting to neuraminidase (NA) of the 2009 H1N1 influenza A virus. NA is an influenza virus structural protein with enzymatic activity of the cleavage of HA-sialic acid interaction to release new viral particles from cells. A model of HIV-1 (pNL4-3.Luc.R(-)E(-)) based pseudovirions packed with HA [hemagglutinin, A/VietNam/1203/2004 (H5N1)] and NA [A/California/04/2009 (H1N1)] was established to evaluate compounds activities on NA function. The viral release can be blocked by neuraminidase inhibitors, oseltamivir and oseltamivir carboxylate, with IC50 of (61 +/- 31) nmol L(-1) and (5.5 +/- 2.9) nmol L(-1) respectively. A point mutation of H275Y on NA leads oseltamivir-resistance. This corresponding mutation was introduced into the system which was also confirmed by oseltamivir and oseltamivir carboxylate.

摘要

本研究旨在建立一种针对2009年甲型H1N1流感病毒神经氨酸酶（NA）的细胞模型。NA是一种流感病毒结构蛋白，具有裂解HA-唾液酸相互作用以从细胞中释放新病毒颗粒的酶活性。建立了一种基于HIV-1（pNL4-3.Luc.R(-)E(-)）的假病毒模型，其包装有HA[血凝素，A/越南/1203/2004（H5N1）]和NA[A/加利福尼亚/04/2009（H1N1）]，以评估化合物对NA功能的活性。神经氨酸酶抑制剂奥司他韦和奥司他韦羧酸盐可阻断病毒释放，IC50分别为(61±31)nmol L(-1)和(5.5±2.9)nmol L(-1)。NA上的H275Y点突变导致对奥司他韦耐药。将该相应突变引入该系统，这也通过奥司他韦和奥司他韦羧酸盐得到证实。