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

被引:27
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
    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.
    [J]. 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
    Das, Kalyan
    Aramini, James M.
    Ma, Li-Chung
    Krug, Robert M.
    Arnold, Eddy
    [J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (05) : 530 - 538
  • [3] Brief report - Oseltamivir resistance during treatment of influenza A (H5N1) infection
    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
    [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
    Deng, T
    Sharps, J
    Fodor, E
    Brownlee, GG
    [J]. JOURNAL OF VIROLOGY, 2005, 79 (13) : 8669 - 8674
  • [5] Peptide-mediated interference with influenza A virus polymerase
    Ghanem, Alexander
    Mayer, Daniel
    Chase, Geoffrey
    Tegge, Werner
    Frank, Ronald
    Kochs, Georg
    Garcia-Sastre, Adolfo
    Schwemmle, Martin
    [J]. JOURNAL OF VIROLOGY, 2007, 81 (14) : 7801 - 7804
  • [6] Crystal structure of the polymerase PAC-PB1N complex from an avian influenza H5N1 virus
    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
    [J]. NATURE, 2008, 454 (7208) : 1123 - U51
  • [7] Detection and Characterization of Influenza A Virus PA-PB2 Interaction through a Bimolecular Fluorescence Complementation Assay
    Hemerka, Joseph N.
    Wang, Dan
    Weng, Yuejin
    Lu, Wuxun
    Kaushik, Radhey S.
    Jin, Jing
    Harmon, Aaron F.
    Li, Feng
    [J]. 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
    Maenz, Benjamin
    Goetz, Veronika
    Wunderlich, Kerstin
    Eisel, Jessica
    Kirchmair, Johannes
    Stech, Juergen
    Stech, Olga
    Chase, Geoffrey
    Frank, Ronald
    Schwemmle, Martin
    [J]. 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
    Pilger, BD
    Cui, C
    Coen, DM
    [J]. CHEMISTRY & BIOLOGY, 2004, 11 (05): : 647 - 654