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

被引:87
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
[71]   The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of α1→2 mannose residues on the outer face of gp120 [J].
Scanlan, CN ;
Pantophlet, R ;
Wormald, MR ;
Saphire, EO ;
Stanfield, R ;
Wilson, IA ;
Katinger, H ;
Dwek, RA ;
Rudd, PM ;
Burton, DR .
JOURNAL OF VIROLOGY, 2002, 76 (14) :7306-7321
[72]   Multisite and multivalent binding between cyanovirin-N and branched oligomannosides: Calorimetric and NMR characterization [J].
Shenoy, SR ;
Barrientos, LG ;
Ratner, DM ;
O'Keefe, BR ;
Seeberger, PH ;
Gronenborn, AM ;
Boyd, MR .
CHEMISTRY & BIOLOGY, 2002, 9 (10) :1109-1118
[73]  
Shenoy SR, 2001, J PHARMACOL EXP THER, V297, P704
[74]   Development of a preventive vaccine for Ebola virus infection in primates [J].
Sullivan, NJ ;
Sanchez, A ;
Rollin, PE ;
Yang, ZY ;
Nabel, GJ .
NATURE, 2000, 408 (6812) :605-609
[75]   Cyanovirin-N gel as a topical microbicide prevents rectal transmission of SHIV89.6P in macaques [J].
Tsai, CC ;
Emau, P ;
Jiang, YH ;
Tian, BP ;
Morton, WR ;
Gustafson, KR ;
Boyd, MR .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 2003, 19 (07) :535-541
[76]   Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models [J].
Tsai, CC ;
Emau, P ;
Jiang, YH ;
Agy, MB ;
Shattock, RJ ;
Schmidt, A ;
Morton, WR ;
Gustafson, KR ;
Boyd, MR .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 2004, 20 (01) :11-18
[77]   Considerations and development of topical microbicides to inhibit the sexual transmission of HIV [J].
Turpin, JA .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2002, 11 (08) :1077-1097
[78]   Prophylactic contraceptives for HIV/AIDS [J].
Uckun, FM ;
D'Cruz, OJ .
HUMAN REPRODUCTION UPDATE, 1999, 5 (05) :506-514
[79]   DNA vaccines expressing either the GP or NP genes of Ebola virus protect mice from lethal challenge [J].
Vanderzanden, L ;
Bray, M ;
Fuller, D ;
Roberts, T ;
Custer, D ;
Spik, K ;
Jahrling, P ;
Huggins, J ;
Schmaljohn, A ;
Schmaljohn, C .
VIROLOGY, 1998, 246 (01) :134-144
[80]   Sexual transmission of HIV in Africa - Other routes of infection are not the dominant contributor to the African epidemic. [J].
Walker, PR ;
Worobey, M ;
Rambaut, A ;
Holmes, EC ;
Pybus, OG .
NATURE, 2003, 422 (6933) :679-679