Structural basis for oseltamivir resistance of influenza viruses

被引：92

作者：

Collins, P. J. ^{[1
]}

Haire, L. F. ^{[1
]}

Lin, Y. P. ^{[1
]}

Liu, J. ^{[1
]}

Russell, R. J. ^{[2
]}

Walker, P. A. ^{[1
]}

Martin, S. R. ^{[1
]}

Daniels, R. S. ^{[1
]}

Gregory, V. ^{[1
]}

Skehel, J. J. ^{[1
]}

Gamblin, S. J. ^{[1
]}

Hay, A. J. ^{[1
]}

机构：

[1] Natl Inst Med Res, MRC, London NW7 1AA, England

[2] Univ St Andrews, Interdisciplinary Ctr Human & Avian Influenza Res, Sch Biol, St Andrews KY16 9ST, Fife, Scotland

来源：

VACCINE | 2009年 / 27卷 / 45期

基金：

英国医学研究理事会;

关键词：

Influenza H5N1; Oseltamivir resistance; H275Y mutation; NEURAMINIDASE INHIBITORS; AVIAN INFLUENZA; IN-VITRO; DESIGN; REPLICATION; SEASON; VIVO; FLU;

D O I：

10.1016/j.vaccine.2009.07.017

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Oseltamivir, one of the two anti-neuraminidase drugs, is currently the most widely used drug against influenza. Resistance to the drug has occurred infrequently among different viruses in response to drug treatment, including A H5N1 viruses, but most notably has emerged among recently circulating A H1N1 viruses and has spread throughout the population in the absence of drug use. Crystal structures of enzyme-drug Complexes, together with enzymatic properties, of mutants of H5N1 neuraminidase have provided explanations for high level oseltamivir resistance due to the common H275Y mutation, with retention of zanamivir susceptibility, and intermediate level resistance due to the N295S mutation. Complementation of enhanced NA activity due to a D344N mutation by the H275Y mutation suggests an explanation for the recent emergence and predominance of oseltamivir-resistant influenza A H1N1 viruses. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：6317 / 6323

页数：7

共 26 条

[1] The interaction of neuraminidase and hemagglutinin mutations in influenza virus in resistance to 4-guanidino-Neu5Ac2en [J].