Identification of influenza virus inhibitors which disrupt of viral polymerase protein-protein interactions

被引:28
作者
Chase, Geoffrey [1 ]
Wunderlich, Kerstin [1 ]
Reuther, Peter [1 ]
Schwemmle, Martin [1 ]
机构
[1] Univ Freiburg Klinikum, Dept Virol, Freiburg, Germany
关键词
Influenza; Polymerase; Antiviral; ELISA; A VIRUS; STRUCTURAL BASIS; RNA-POLYMERASE; SMALL-MOLECULE; COMPLEX; REPLICATION; PEPTIDE;
D O I
10.1016/j.ymeth.2011.08.007
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Due to their ability to rapidly mutate, influenza viruses quickly develop resistance against many antiviral substances, leading to an urgent need for new compounds. The trimeric viral polymerase complex, a major target for the development of new inhibitors, must be assembled from the PB1, PB2, and PA subunits for successful infection. Here, we describe ELISA-based assays which allow the identification of peptides which impair polymerase complex formation. Since the protein-protein interaction domains of the viral polymerase are highly conserved, these inhibitors are also predicted to be active against a broad range of influenza strains. Using this method, identification of small molecules and lead compounds against influenza A and B viruses should be feasible. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:188 / 191
页数:4
相关论文
共 16 条
[1]   Structural basis for suppression of a host antiviral response by influenza A virus [J].
Das, Kalyan ;
Ma, Li-Chung ;
Xiao, Rong ;
Radvansky, Brian ;
Aramini, James ;
Zhao, Li ;
Marklund, Jesper ;
Kuo, Rei-Lin ;
Twu, Karen Y. ;
Arnold, Eddy ;
Krug, Robert M. ;
Montelione, Gaetano T. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (35) :13093-13098
[2]   Structures of influenza A proteins and insights into antiviral drug targets [J].
Das, Kalyan ;
Aramini, James M. ;
Ma, Li-Chung ;
Krug, Robert M. ;
Arnold, Eddy .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (05) :530-538
[3]   Brief report - Oseltamivir resistance during treatment of influenza A (H5N1) infection [J].
de Jong, MD ;
Thanh, TT ;
Khanh, TH ;
Hien, VM ;
Smith, GJD ;
Chau, NV ;
Cam, BV ;
Qui, PT ;
Ha, DQ ;
Guan, Y ;
Peiris, JSM ;
Hien, TT ;
Farrar, J .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (25) :2667-2672
[4]   In vitro assembly of PB2 with a PB1-PA dimer supports a new model of assembly of influenza A virus polymerase subunits into a functional trimeric complex [J].
Deng, T ;
Sharps, J ;
Fodor, E ;
Brownlee, GG .
JOURNAL OF VIROLOGY, 2005, 79 (13) :8669-8674
[5]   Peptide-mediated interference with influenza A virus polymerase [J].
Ghanem, Alexander ;
Mayer, Daniel ;
Chase, Geoffrey ;
Tegge, Werner ;
Frank, Ronald ;
Kochs, Georg ;
Garcia-Sastre, Adolfo ;
Schwemmle, Martin .
JOURNAL OF VIROLOGY, 2007, 81 (14) :7801-7804
[6]   Crystal structure of the polymerase PAC-PB1N complex from an avian influenza H5N1 virus [J].
He, Xiaojing ;
Zhou, Jie ;
Bartlam, Mark ;
Zhang, Rongguang ;
Ma, Jianyuan ;
Lou, Zhiyong ;
Li, Xuemei ;
Li, Jingjing ;
Joachimiak, Andrzej ;
Zeng, Zonghao ;
Ge, Ruowen ;
Rao, Zihe ;
Liu, Yingfang .
NATURE, 2008, 454 (7208) :1123-U51
[7]   Detection and Characterization of Influenza A Virus PA-PB2 Interaction through a Bimolecular Fluorescence Complementation Assay [J].
Hemerka, Joseph N. ;
Wang, Dan ;
Weng, Yuejin ;
Lu, Wuxun ;
Kaushik, Radhey S. ;
Jin, Jing ;
Harmon, Aaron F. ;
Li, Feng .
JOURNAL OF VIROLOGY, 2009, 83 (08) :3944-3955
[8]   Disruption of the Viral Polymerase Complex Assembly as a Novel Approach to Attenuate Influenza A Virus [J].
Maenz, Benjamin ;
Goetz, Veronika ;
Wunderlich, Kerstin ;
Eisel, Jessica ;
Kirchmair, Johannes ;
Stech, Juergen ;
Stech, Olga ;
Chase, Geoffrey ;
Frank, Ronald ;
Schwemmle, Martin .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (10) :8414-8424
[9]  
Obayashi E, 2008, NATURE, V454, P1127, DOI [10.1038/nature07225, 10.5940/jcrsj.50.329]
[10]   Identification of a small molecule that inhibits herpes simplex virus DNA polymerase subunit interactions and viral replication [J].
Pilger, BD ;
Cui, C ;
Coen, DM .
CHEMISTRY & BIOLOGY, 2004, 11 (05) :647-654