Establishment of a cell-based 2009 H1N1 influenza neuraminidase inhibitors evaluation system.
- Author:
Chao ZHANG
1
;
Ying-li CAO
;
Wu ZHONG
;
Jun-hai XIAO
;
Ying GUO
Author Information
1. Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Cell Line, Tumor;
Drug Resistance, Viral;
genetics;
Enzyme Inhibitors;
pharmacology;
HEK293 Cells;
HIV-1;
genetics;
Hemagglutinin Glycoproteins, Influenza Virus;
genetics;
metabolism;
Humans;
Influenza A Virus, H1N1 Subtype;
drug effects;
genetics;
metabolism;
Influenza A Virus, H5N1 Subtype;
drug effects;
genetics;
metabolism;
Mutation;
Neuraminidase;
antagonists & inhibitors;
genetics;
metabolism;
Oseltamivir;
analogs & derivatives;
pharmacology;
Plasmids;
Transfection;
Virus Internalization
- From:
Acta Pharmaceutica Sinica
2010;45(3):383-387
- CountryChina
- Language:Chinese
-
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.
