The highly specific carbohydrate-binding protein cyanovirin-N: Structure, anti-HIV/Ebola activity and possibilities for therapy

被引:86
作者
Barrientos, LG [1 ]
Gronenborn, AM [1 ]
机构
[1] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA
关键词
cyanovirin-N; HIV; GP120; Ebola; GP(1,2); SARS; microbicidal agent; high-mannose oligosaccharides;
D O I
10.2174/1389557053402783
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Cyanovirin-N (CV-N), a cyanobacterial lectin, is a potent viral entry inhibitor currently under development as a microbicide against a broad spectrum of enveloped viruses. CV-N was originally identified as a highly active anti-HIV agent and later, as a virucidal agent against other unrelated enveloped viruses Such as Ebola, and possibly other viruses. CV-N's antiviral activity appears to involve unique recognition of N-linked high-mannose oligosaccharides, Man-8 and Man-9, on the viral surface glycoproteins. Due to its distinct mode of action and opportunities for harnessing the associated interaction for therapeutic intervention, a substantial body of research on CV-N has accumulated since its discovery in 1997. In this review we focus in particular on structural studies on CV-N and their relationship to biological activity.
引用
收藏
页码:21 / 31
页数:11
相关论文
共 87 条
[1]   In vitro evaluation of cyanovirin-N antiviral activity, by use of lentiviral vectors pseudotyped with filovirus envelope glycoproteins [J].
Barrientos, LG ;
Lasala, F ;
Otero, JR ;
Sanchez, A ;
Delgado, R .
JOURNAL OF INFECTIOUS DISEASES, 2004, 189 (08) :1440-1443
[2]   Solution structure of a circular-permuted variant of the potent HIV-inactivating protein cyanovirin-N: Structural basis for protein stability and oligosaccharide interaction [J].
Barrientos, LG ;
Louis, JM ;
Ratner, DM ;
Seeberger, PH ;
Gronenborn, AM .
JOURNAL OF MOLECULAR BIOLOGY, 2003, 325 (01) :211-223
[3]   Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus [J].
Barrientos, LG ;
O'Keefe, BR ;
Bray, M ;
Anthony, S ;
Gronenborn, AM ;
Boyd, MR .
ANTIVIRAL RESEARCH, 2003, 58 (01) :47-56
[4]   Design and initial characterization of a circular permuted variant of the potent HIV-inactivating protein cyanovirin-N [J].
Barrientos, LG ;
Louis, JM ;
Hung, J ;
Smith, TH ;
O'Keefe, BR ;
Gardella, RS ;
Mori, T ;
Boyd, MR ;
Gronenborn, AM .
PROTEINS-STRUCTURE FUNCTION AND GENETICS, 2002, 46 (02) :153-160
[5]   The domain-swapped dimer of cyanovirin-N is in a metastable folded state: Reconciliation of X-ray and NMR structures [J].
Barrientos, LG ;
Louis, JM ;
Botos, I ;
Mori, T ;
Han, ZZ ;
O'Keefe, BR ;
Boyd, MR ;
Wlodawer, A ;
Gronenborn, AM .
STRUCTURE, 2002, 10 (05) :673-686
[6]   The domain-swapped dimer of cyanovirin-N contains two sets of oligosaccharide binding sites in solution [J].
Barrientos, LG ;
Gronenborn, AM .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 298 (04) :598-602
[7]   Structural characterization of the dilute aqueous surfactant solution of cetylpyridinium bromide/hexanol/sodium bromide [J].
Barrientos, LG ;
Gawrisch, K ;
Cheng, N ;
Steven, AC ;
Gronenborn, AM .
LANGMUIR, 2002, 18 (10) :3773-3779
[8]   Letter to the Editor:: 1H, 13C, 15N resonance assignments and fold verification of a circular permuted variant of the potent HIV-inactivating protein cyanovirin-N* [J].
Barrientos, LG ;
Campos-Olivas, R ;
Louis, JM ;
Fiser, A ;
Sali, A ;
Gronenborn, AM .
JOURNAL OF BIOMOLECULAR NMR, 2001, 19 (03) :289-290
[9]   REFINED STRUCTURE OF MONOMERIC DIPHTHERIA-TOXIN AT 2.3-ANGSTROM RESOLUTION [J].
BENNETT, MJ ;
EISENBERG, D .
PROTEIN SCIENCE, 1994, 3 (09) :1464-1475
[10]   High throughput screening for cyanovirin-N mimetics binding to HIV-1 gp41 [J].
Beutler, JA ;
McMahon, JB ;
Johnson, TR ;
O'Keefe, BR ;
Buzzell, RA ;
Robbins, D ;
Gardella, R ;
Wilson, J ;
Boyd, MR .
JOURNAL OF BIOMOLECULAR SCREENING, 2002, 7 (02) :105-110