Novel hemagglutinin inhibitors for H1N1 influenza virus screening from TCM database

被引：11

作者：

Chang, Tung-Ti ^{[1
,2
]}

Sun, Mao-Feng ^{[1
,3
]}

Chen, Hsin-Yi ^{[4
]}

Tsai, Fuu-Jen ^{[4
,5
]}

Fisher, Mark ^{[6
]}

Lin, Jaung-Geng ^{[1
]}

Chen, Calvin Yu-Chian ^{[1
,4
,6
,7
]}

机构：

[1] China Med Univ, Sch Chinese Med, Lab Computat & Syst Biol, Taichung 40402, Taiwan

[2] China Med Univ Hosp, Dept Chinese Pediat, Taichung 40402, Taiwan

[3] China Med Univ Hosp, Dept Acupuncture, Taichung 40402, Taiwan

[4] Asia Univ, Dept Bioinformat, Taichung 41354, Taiwan

[5] China Med Univ, Dept Med Genet, Taichung 40402, Taiwan

[6] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA

[7] MIT, Cambridge, MA 02139 USA

来源：

MOLECULAR SIMULATION | 2011年 / 37卷 / 05期

关键词：

H1N1; Tamiflu; docking; structure-based drug design; traditional Chinese medicine; PHARMACOPHORE ANALYSIS; DRUG DESIGN; PHARMACOINFORMATICS APPROACH; MOLECULAR SIMULATION; RESISTANT INFLUENZA; ANTIGENIC DRIFT; A RECEPTOR; ACID; OSELTAMIVIR; DISCOVERY;

D O I：

10.1080/08927022.2010.543973

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070305 [高分子化学与物理];

摘要：

The emergence of Tamiflu (oseltamivir)-resistant viral strains in pandemic of H1N1/09 influenza virus has raised global awareness of anti-viral drug resistant issue. There is an urgent demand for developing new anti-influenza compound. The purpose of this research is to design novel haemagglutinin (HA) inhibitor for inhibiting viral entry into the host cell. We performed structure-based drug design to analyse interactions between the potent inhibitor and HA. A traditional Chinese medicine (TCM) database was used for in silico screening process. The docked TCM constituents were input into de novo evolution to generate derivatives. Selected derivatives were then docked back to HA binding site. We identify four key features from top 10 docked derivatives' binding conformations and structure scaffolds. The addition of 2-aminopyridinium group has the greatest influence in the binding ability of TCM derivatives and is, therefore, suggested to be the key point in designing HA inhibitors.

引用

页码：361 / 368

页数：8

共 43 条

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Prediction of protein conformation in water and on surfaces by Monte Carlo simulations using united-atom method [J].