Algal lectins as potential HIV microbicide candidates

Marine Drugs

Volumn 10, Issue 7, 2012, Pages 1476-1497

  Huskens, Dana ^a   Schols, Dominique ^a  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

Algae; Carbohydrate binding agents; Gp120 envelope; HIV; Lectin; Microbicide; Virus entry

Indexed keywords

ANTIVIRUS AGENT; CYANOVIRIN N; GRIFFITHSIN; LECTIN; MICROBICIDE; MICROCYSTIS VIRIDIS LECTIN; MICROVIRIN; NONOXINOL 9; OSCILLATORIA AGARDHII AGGLUTININ; SCYTOVIRIN; UNCLASSIFIED DRUG;

ALGA; ANTIVIRAL ACTIVITY; CONCENTRATION RESPONSE; DRUG MECHANISM; DRUG SAFETY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; NONHUMAN; REVIEW; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; STRUCTURE ANALYSIS; VIRUS RESISTANCE; VIRUS TRANSMISSION;

ALGAE; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; MICROCYSTIS VIRIDIS; PLANKTOTHRIX AGARDHII;

EID: 84864380840     PISSN: None     EISSN: 16603397     Source Type: Journal    
DOI: 10.3390/md10071476     Document Type: Review

References (100)

1. Pool, R.; Hart, G.; Green, G.; Harrison, S.; Nyanzi, S.; Whitworth, J. Men's attitudes to condoms and female controlled means of protection against HIV and STDs in south-western Uganda. Cult. Health Sex 2000, 2, 197-211.
2. Buckheit, R.W., Jr.; Watson, K.M.; Morrow, K.M.; Ham, A.S. Development of topical microbicides to prevent the sexual transmission of HIV. Antivir. Res. 2010, 85, 142-158.
3. Abdool, K.Q.; Abdool Karim, S.S.; Frohlich, J.A.; Grobler, A.C.; Baxter, C.; Mansoor, L.E.; Kharsany, A.B.; Sibeko, S.; Mlisana, K.P.; Omar, Z.; et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010, 329, 1168-1174.
4. Kwong, P.D.; Wyatt, R.; Robinson, J.; Sweet, R.W.; Sodroski, J.; Hendrickson, W.A. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 1998, 393, 648-659. (Pubitemid 28289647)
5. Leonard, C.K.; Spellman, M.W.; Riddle, L.; Harris, R.J.; Thomas, J.N.; Gregory, T.J. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J. Biol. Chem. 1990, 265, 10373-10382.
6. Wyatt, R.; Kwong, P.D.; Desjardins, E.; Sweet, R.W.; Robinson, J.; Hendrickson, W.A.; Sodroski, J.G. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature 1998, 393, 705-711. (Pubitemid 28289663)
7. Go, E.P.; Irungu, J.; Zhang, Y.; Dalpathado, D.S.; Liao, H.X.; Sutherland, L.L.; Alam, S.M.; Haynes, B.F.; Desaire, H. Glycosylation site-specific analysis of HIV envelope proteins (JR-FL and CON-S) reveals major differences in glycosylation site occupancy, glycoform profiles, and antigenic epitopes' accessibility. J. Proteome Res. 2008, 7, 1660-1674.
8. Zhu, X.; Borchers, C.; Bienstock, R.J.; Tomer, K.B. Mass spectrometric characterization of the glycosylation pattern of HIV-gp120 expressed in CHO cells. Biochemistry 2000, 39, 11194-11204.
9. Helenius, A.; Aebi, M. Intracellular functions of N-linked glycans. Science 2001, 291, 2364-2369. (Pubitemid 32231791)
10. Sanders, R.W.; Venturi, M.; Schiffner, L.; Kalyanaraman, R.; Katinger, H.; Lloyd, K.O.; Kwong, P.D.; Moore, J.P. The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120. J. Virol. 2002, 76, 7293-7305.
11. Scanlan, C.N.; Offer, J.; Zitzmann, N.; Dwek, R.A. Exploiting the defensive sugars of HIV-1 for drug and vaccine design. Nature 2007, 446, 1038-1045. (Pubitemid 46676066)
12. Weis, W.I.; Taylor, M.E.; Drickamer, K. The C-type lectin superfamily in the immune system. Immunol. Rev. 1998, 163, 19-34. (Pubitemid 28327859)
13. Lavine, C.L.; Lao, S.; Montefiori, D.C.; Haynes, B.F.; Sodroski, J.G.; Yang, X.Z. High-mannose glycan-dependent epitopes are frequently targeted in broad neutralizing antibody responses during human immunodeficiency virus type 1 infection. J. Virol. 2012, 86, 2153-2164.
14. Walker, L.M.; Sok, D.; Nishimura, Y.; Donau, O.; Sadjadpour, R.; Gautam, R.; Shingai, M.; Pejchal, R.; Ramos, A.; Simek, M.D.; et al. Rapid development of glycan-specific, broad, and potent anti-HIV-1 gp120 neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque. Proc. Natl. Acad. Sci. USA 2011, 108, 20125-20129.
15. Boyd, M.R.; Gustafson, K.R.; McMahon, J.B.; Shoemaker, R.H.; O'Keefe, B.R.; Mori, T.; Gulakowski, R.J.; Wu, L.; Rivera, M.I.; Laurencot, C.M.; et al. Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: Potential applications to microbicide development. Antimicrob. Agents Chemother. 1997, 41, 1521-1530.
16. Gustafson, K.R.; Sowder, R.C.; Henderson, L.E.; Cardellina, J.H.; McMahon, J.B.; Rajamani, U.; Pannell, L.K.; Boyd, M.R. Isolation, primary sequence determination, and disulfide bond structure of cyanovirin-N, an anti-HIV (human immunodeficiency virus) protein from the cyanobacterium Nostoc ellipsosporum. Biochem. Biophys. Res. Commun. 1997, 238, 223-228. (Pubitemid 27453305)
17. Bewley, C.A.; Gustafson, K.R.; Boyd, M.R.; Covell, D.G.; Bax, A.; Clore, G.M.; Gronenborn, A.M. Solution structure of cyanovirin-N, a potent HIV-inactivating protein. Nat. Struct. Biol. 1998, 5, 571-578.
18. Bewley, C.A. Solution structure of a cyanovirin-N: Manα1- 2Manα complex: Structural basis for high-affinity carbohydrate-mediated binding to gp120. Structure 2001, 9, 931-940. (Pubitemid 32972159)
19. Liu, Y.; Carroll, J.R.; Holt, L.A.; McMahon, J.; Giomarelli, B.; Ghirlanda, G. Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Biopolymers 2009, 92, 194-200.
20. Bewley, C.A.; Otero-Quintero, S. The potent anti-HIV protein cyanovirin-N contains two novel carbohydrate binding sites that selectively bind to Man(8) D1D3 and Man(9) with nanomolar affinity: Implications for binding to the HIV envelope protein gp120. J. Am. Chem. Soc. 2001, 123, 3892-3902. (Pubitemid 32899476)
21. Botos, I.; O'Keefe, B.R.; Shenoy, S.R.; Cartner, L.K.; Ratner, D.M.; Seeberger, P.H.; Boyd, M.R.; Wlodawer, A. Structures of the complexes of a potent anti-HIV protein cyanovirin-N and high mannose oligosaccharides. J. Biol. Chem. 2002, 277, 34336-34342.
22. Kehr, J.C.; Zilliges, Y.; Springer, A.; Disney, M.D.; Ratner, D.D.; Bouchier, C.; Seeberger, P.H.; de Marsac, N.T.; Dittmann, E. A mannan binding lectin is involved in cell-cell attachment in a toxic strain of Microcystis aeruginosa. Mol. Microbiol. 2006, 59, 893-906.
23. Shahzad-Ul-Hussan, S.; Gustchina, E.; Ghirlando, R.; Clore, G.M.; Bewley, C.A. Solution structure of the monovalent lectin microvirin in complex with Man(alpha)(1-2)Man provides a basis for anti-HIV activity with low toxicity. J. Biol. Chem. 2011, 286, 20788-20796.
24. Yamaguchi, M.; Ogawa, T.; Muramoto, K.; Kamio, Y.; Jimbo, M.; Kamiya, H. Isolation and characterization of a mannan-binding lectin from the freshwater cyanobacterium (blue-green algae) Microcystis viridis. Biochem. Biophys. Res. Commun. 1999, 265, 703-708.
25. Williams, D.C., Jr.; Lee, J.Y.; Cai, M.; Bewley, C.A.; Clore, G.M. Crystal structures of the HIV-1 inhibitory cyanobacterial protein MVL free and bound to Man3GlcNAc2: Structural basis for specificity and high-affinity binding to the core pentasaccharide from N-linked oligomannoside. J. Biol. Chem. 2005, 280, 29269-29276. (Pubitemid 41161381)
26. Bokesch, H.R.; O'Keefe, B.R.; McKee, T.C.; Pannell, L.K.; Patterson, G.M.; Gardella, R.S.; Sowder, R.C.; Turpin, J.; Watson, K.; Buckheit, R.W., Jr.; Boyd, M.R. A potent novel anti-HIV protein from the cultured cyanobacterium Scytonema varium. Biochemistry 2003, 42, 2578-2584. (Pubitemid 36330611)
27. Moulaei, T.; Botos, I.; Ziolkowska, N.E.; Bokesch, H.R.; Krumpe, L.R.; McKee, T.C.; O'Keefe, B.R.; Dauter, Z.; Wlodawer, A. Atomic-resolution crystal structure of the antiviral lectin scytovirin. Protein Sci. 2007, 16, 2756-2760. (Pubitemid 350172763)
28. Moulaei, T.; Stuchlik, O.; Reed, M.; Yuan, W.; Pohl, J.; Lu, W.; Haugh-Krumpe, L.; O'Keefe, B.R.; Wlodawer, A. Topology of the disulfide bonds in the antiviral lectin scytovirin. Protein Sci. 2010, 19, 1649-1661.
29. Adams, E.W.; Ratner, D.M.; Bokesch, H.R.; McMahon, J.B.; O'Keefe, B.R.; Seeberger, P.H. Oligosaccharide and glycoprotein microarrays as tools in HIV glycobiology; glycan-dependent gp120/protein interactions. Chem. Biol. 2004, 11, 875-881. (Pubitemid 38836903)
30. McFeeters, R.L.; Xiong, C.; O'Keefe, B.R.; Bokesch, H.R.; McMahon, J.B.; Ratner, D.M.; Castelli, R.; Seeberger, P.H.; Byrd, R.A. The novel fold of scytovirin reveals a new twist for antiviral entry inhibitors. J. Mol. Biol. 2007, 369, 451-461. (Pubitemid 46678045)
31. Sato, Y.; Okuyama, S.; Hori, K. Primary structure and carbohydrate binding specificity of a potent anti-HIV lectin isolated from the filamentous cyanobacterium Oscillatoria agardhii. J. Biol. Chem. 2007, 282, 11021-11029. (Pubitemid 47100773)
32. Sato, Y.; Murakami, M.; Miyazawa, K.; Hori, K. Purification and characterization of a novel lectin from a freshwater cyanobacterium, Oscillatoria agardhii. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 2000, 125, 169-177. (Pubitemid 30249243)
33. Koharudin, L.M.; Furey, W.; Gronenborn, A.M. Novel fold and carbohydrate specificity of the potent anti-HIV cyanobacterial lectin from Oscillatoria agardhii. J. Biol. Chem. 2011, 286, 1588-1597.
34. Koharudin, L.M.; Gronenborn, A.M. Structural basis of the anti-HIV activity of the cyanobacterial Oscillatoria agardhii agglutinin. Structure 2011, 19, 1170-1181.
35. Mori, T.; O'Keefe, B.R.; Sowder, R.C.; Bringans, S.; Gardella, R.; Berg, S.; Cochran, P.; Turpin, J.A.; Buckheit, R.W., Jr.; McMahon, J.B.; Boyd, M.R. Isolation and characterization of griffithsin, a novel HIV-inactivating protein, from the red alga Griffithsia sp. J. Biol. Chem. 2005, 280, 9345-9353. (Pubitemid 40409628)
36. Ziolkowska, N.E.; O'Keefe, B.R.; Mori, T.; Zhu, C.; Giomarelli, B.; Vojdani, F.; Palmer, K.E.; McMahon, J.B.; Wlodawer, A. Domain-swapped structure of the potent antiviral protein griffithsin and its mode of carbohydrate binding. Structure 2006, 14, 1127-1135. (Pubitemid 44056021)
37. Ziolkowska, N.E.; Wlodawer, A. Structural studies of algal lectins with anti-HIV activity. Acta Biochim. Pol. 2006, 53, 617-626. (Pubitemid 46090112)
38. Moulaei, T.; Shenoy, S.R.; Giomarelli, B.; Thomas, C.; McMahon, J.B.; Dauter, Z.; O'Keefe, B.R.; Wlodawer, A. Monomerization of viral entry inhibitor griffithsin elucidates the relationship between multivalent binding to carbohydrates and anti-HIV activity. Structure 2010, 18, 1104-1115.
39. Huskens, D.; Schols, D. Rega Institute for Medical Research, KU Leuven, Leuven, Belgium. Unpublished work, 2012.
40. Xiong, S.; Fan, J.; Kitazato, K. The antiviral protein cyanovirin-N: The current state of its production and applications. Appl. Microbiol. Biotechnol. 2010, 86, 805-812.
41. Balzarini, J.; van Laethem, K.; Peumans, W.J.; van Damme, E.J.; Bolmstedt, A.; Gago, F.; Schols, D. Mutational pathways, resistance profile, and side effects of cyanovirin relative to human immunodeficiency virus type 1 strains with N-glycan deletions in their gp120 envelopes. J. Virol. 2006, 80, 8411-8421. (Pubitemid 44384854)
42. Witvrouw, M.; Fikkert, V.; Hantson, A.; Pannecouque, C.; O'Keefe, B.R.; McMahon, J.; Stamatatos, L.; de Clercq, E.; Bolmstedt, A. Resistance of human immunodeficiency virus type 1 to the high-mannose binding agents cyanovirin N and concanavalin A. J. Virol. 2005, 79, 7777-7784. (Pubitemid 40756811)
43. Huskens, D.; Ferir, G.; Vermeire, K.; Kehr, J.C.; Balzarini, J.; Dittmann, E.; Schols, D. Microvirin, a novel alpha(1,2)-mannose-specific lectin isolated from Microcystis aeruginosa, has anti-HIV-1 activity comparable with that of cyanovirin-N but a much higher safety profile. J. Biol. Chem. 2010, 285, 24845-24854.
44. Alexandre, K.B.; Gray, E.S.; Lambson, B.E.; Moore P.L.; Choge, I.A.; Mlisana, K.; Karim, S.S.; McMahon, J.; O'Keefe B.; Chikwamba, R.; Morris, L. Mannose-rich glycosylation patterns on HIV-1 subtype C gp120 and sensitivity to the lectins, griffithsin, cyanovirin-N and scytovirin. Virology 2010, 402, 187-196.
45. Férir, G.; Huskens, D.; Palmer, K.E.; Boudreaux, D.M.; Swanson, M.M.; Markovitz, D.M.; Balzarini, J.; Schols, D. Combinations of griffithsin with other carbohydrate-binding agents (CBAs) demonstrate superior activity against HIV-1, HIV-2 and selected CBA-resistant HIV-1 strains. AIDS Res. Hum. Retroviruses 2012, doi:10.1089/aid.2012.0026.
46. Bewley, C.A.; Cai, M.; Ray, S.; Ghirlando, R.; Yamaguchi, M.; Muramoto, K. New carbohydrate specificity and HIV-1 fusion blocking activity of the cyanobacterial protein MVL: NMR, ITC and sedimentation equilibrium studies. J. Mol. Biol. 2004, 339, 901-914. (Pubitemid 38686352)
47. Xiong, C.Y.; O'Keefe, B.R.; Botos, I.; Wlodawer, A.; McMahon, J.B. Overexpression and purification of scytovirin, a potent, novel anti-HIV protein from the cultured cyanobacterium Scytonema varium. Protein Expr. Purif. 2006, 46, 233-239.
48. Emau, P.; Tian, B.; O'Keefe, B.R.; Mori, T.; McMahon, J.B.; Palmer, K.E.; Jiang, Y.; Bekele, G.; Tsai, C.C. Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti-HIV microbicide. J. Med. Primatol. 2007, 36, 244-253.
49. Férir, G.; Palmer, K.E.; Schols, D. Synergistic activity profile of griffithsin in combination with tenofovir, maraviroc and enfuvirtide against HIV-1 clade C. Virology 2011, 417, 253-258.
50. Kouokam, J.C.; Huskens, D.; Schols, D.; Johannemann, A.; Riedell, S.K.; Walter, W.; Walker, J.M.; Matoba, N.; O'Keefe, B.R.; Palmer, K.E. Investigation of griffithsin's interactions with human cells confirms its outstanding safety and efficacy profile as a microbicide candidate. PLoS One 2011, 6, doi:10.1371/journal.pone.0022635.
51. O'Keefe, B.R.; Vojdani, F.; Buffa, V.; Shattock, R.J.; Montefiori, D.C.; Bakke, J.; Mirsalis, J.; d'Andrea, A.L.; Hume, S.D.; Bratcher, B.; et al. Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component. Proc. Natl. Acad. Sci. USA 2009, 106, 6099-6104.
52. Alexandre, K.B.; Gray, E.S.; Pantophlet, R.; Moore, P.L.; McMahon, J.B.; Chakauya, E.; O'Keefe, B.R.; Chikwamba, R.; Morris, L. Binding of the mannose-specific lectin, griffithsin, to HIV-1 gp120 exposes the CD4-binding site. J. Virol. 2011, 85, 9039-9050.
53. Hladik, F.; Hope, T.J. HIV infection of the genital mucosa in women. Curr. HIV/AIDS Rep. 2009, 6, 20-28.
54. De Jong, M.A.; Geijtenbeek, T.B. Human immunodeficiency virus-1 acquisition in genital mucosa: Langerhans cells as key-players. J. Intern. Med. 2009, 265, 18-28.
55. Haase, A.T. Targeting early infection to prevent HIV-1 mucosal transmission. Nature 2010, 464, 217-223.
56. Hladik, F.; McElrath, M.J. Setting the stage: Host invasion by HIV. Nat. Rev. Immunol. 2008, 8, 447-457. (Pubitemid 351735878)
57. Yu, H.J.; Reuter, M.A.; McDonald, D. HIV traffics through a specialized, surface-accessible intracellular compartment during trans-infection of T cells by mature dendritic cells. PLoS Pathog. 2008, 4, doi: 10.1371/journal.ppat. 1000134.
58. Cavrois, M.; Neidleman, J.; Greene, W.C. The Achilles heel of the Trojan horse model of HIV-1 trans-infection. PLoS Pathog. 2008, 4, doi:10.1371/journal. ppat.1000051.
59. Piguet, V.; Sattentau, Q. Dangerous liaisons at the virological synapse. J. Clin. Invest. 2004, 114, 605-610. (Pubitemid 39578747)
60. Pohlmann, S.; Baribaud, F.; Doms, R.W. DC-SIGN and DC-SIGNR: Helping hands for HIV. Trends Immunol. 2001, 22, 643-646. (Pubitemid 34008592)
61. Burleigh, L.; Lozach, P.Y.; Schiffer, C.; Staropoli, I.; Pezo, V.; Porrot, F.; Canque, B.; Virelizier, J.L.; Arenzana-Seisdedos, F.; Amara, A. Infection of dendritic cells (DCs), not DC-SIGN-mediated internalization of human immunodeficiency virus, is required for long-term transfer of virus to T cells. J. Virol. 2006, 80, 2949-2957. (Pubitemid 43346390)
62. Buffa, V.; Stieh, D.; Mamhood, N.; Hu, Q.; Fletcher, P.; Shattock, R.J. Cyanovirin-N potently inhibits human immunodeficiency virus type 1 infection in cellular and cervical explant models. J. Gen. Virol. 2009, 90, 234-243.
63. Alexandre, K.B.; Gray, E.S.; Mufhandu, H.; McMahon, J.B.; Chakauya, E.; O'Keefe, B.R.; Chikwamba, R.; Morris, L. The lectins griffithsin, cyanovirin-N and scytovirin inhibit HIV-1 binding to the DC-SIGN receptor and transfer to CD4+ cells. Virology 2012, 423, 175-186.
64. Balzarini, J.; van Herrewege, Y.; Vermeire, K.; Vanham, G.; Schols, D. Carbohydrate-binding agents efficiently prevent dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-directed HIV-1 transmission to T lymphocytes. Mol. Pharmacol. 2007, 71, 3-11. (Pubitemid 46020972)
65. Hu, Q.X.; Frank, I.; Williams, V.; Santos, J.J.; Watts, P.; Griffin, G.E.; Moore, J.R.; Pope, M.; Shattock, R.J. Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue. J. Exp. Med. 2004, 199, 1065-1075. (Pubitemid 38619903)
66. Fischetti, L.; Barry, S.M.; Hope, T.J.; Shattock, R.J. HIV-1 infection of human penile explant tissue and protection by candidate microbicides. AIDS 2009, 23, 319-328.
67. Tsai, C.C.; Emau, P.; Jiang, Y.; Agy, M.B.; Shattock, R.J.; Schmidt, A.; Morton, W.R.; Gustafson, K.R.; Boyd, M.R. Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models. AIDS Res. Hum. Retroviruses 2004, 20, 11-18. (Pubitemid 38147172)
68. Tsai, C.C.; Emau, P.; Jiang, Y.; Tian, B.; Morton, W.R.; Gustafson, K.R.; Boyd, M.R. Cyanovirin-N gel as a topical microbicide prevents rectal transmission of SHIV89.6P in macaques. AIDS Res. Hum. Retroviruses 2003, 19, 535-541. (Pubitemid 36900571)
69. Lagenaur, L.A.; Sanders-Beer, B.E.; Brichacek, B.; Pal, R.; Liu, X.; Liu, Y.; Yu, R.; Venzon, D.; Lee, P.P.; Hamer, D.H. Prevention of vaginal SHIV transmission in macaques by a live recombinant Lactobacillus. Mucosal Immunol. 2011, 4, 648-657.
70. Blower, S.; Ma, L. Calculating the contribution of herpes simplex virus type 2 epidemics to increasing HIV incidence: Treatment implications. Clin. Infect. Dis. 2004, 39, S240-S247. (Pubitemid 39447299)
71. Buve, A. Can we reduce the spread of HIV infection by suppressing herpes simplex virus type 2 infection? F1000 Med. Rep. 2010, 2, doi:10.3410/M2-41.
72. Corey, L. Synergistic copathogens - HIV-1 and HSV-2. N. Engl. J. Med. 2007, 356, 854-856. (Pubitemid 46294619)
73. Balzarini, J. Carbohydrate-binding agents: A potential future cornerstone for the chemotherapy of enveloped viruses? Antivir. Chem. Chemother. 2007, 18, 1-11. (Pubitemid 46426933)
74. Helle, F.; Wychowski, C.; Vu-Dac, N.; Gustafson, K.R.; Voisset, C.; Dubuisson, J. Cyanovirin-N inhibits hepatitis C virus entry by binding to envelope protein glycans. J. Biol. Chem. 2006, 281, 25177-25183. (Pubitemid 44401904)
75. O'Keefe, B.R.; Smee, D.F.; Turpin, J.A.; Saucedo, C.J.; Gustafson, K.R.; Mori, T.; Blakeslee, D.; Buckheit, R.; Boyd, M.R. Potent anti-influenza activity of cyanovirin-N and interactions with viral hemagglutinin. Antimicrob. Agents Chemother. 2003, 47, 2518-2525. (Pubitemid 36919454)
76. Barrientos, L.G.; O'Keefe, B.R.; Bray, M.; Anthony, S.; Gronenborn, A.M.; Boyd, M.R. Cyanovirin-N binds to the viral surface glycoprotein, GP(1,2) and inhibits infectivity of Ebola virus. Antivir. Res. 2003, 58, 47-56. (Pubitemid 36507221)
77. Smee, D.F.; Bailey, K.W.; Wong, M.H.; O'Keefe, B.R.; Gustafson, K.R.; Mishin, V.P.; Gubareva, L.V. Treatment of influenza A (H1N1) virus infections in mice and ferrets with cyanovirin-N. Antiviral Res. 2008, 80, 266-271.
78. Dey, B.; Lerner, D.L.; Lusso, P.; Boyd, M.R.; Elder, J.H.; Berger, E.A. Multiple antiviral activities of cyanovirin-N: Blocking of human immunodeficiency virus type 1 gp120 interaction with CD4 and coreceptor and inhibition of diverse enveloped viruses. J. Virol. 2000, 74, 4562-4569. (Pubitemid 30237881)
79. Meuleman, P.; Albecka, A.; Belouzard, S.; Vercauteren, K.; Verhoye, L.; Wychowski, C.; Leroux-Roels, G.; Palmer, K.E.; Dubuisson, J. Griffithsin has antiviral activity against hepatitis C virus. Antimicrob. Agents Chemother. 2011, 55, 5159-5167.
80. O'Keefe, B.R.; Giomarelli, B.; Barnard, D.L.; Shenoy, S.R.; Chan, P.K.S.; McMahon, J.B.; Palmer, K.E.; Barnett, B.W.; Meyerholz, D.K.; Wohlford-Lenane, C.L.; Mccray, P.B. Broad-spectrum in vitro activity and in vivo efficacy of the antiviral protein griffithsin against emerging viruses of the family Coronaviridae. J. Virol. 2010, 84, 2511-2521.
81. Benes, S.; Mccormack, W.M. Inhibition of growth of Chlamydia trachomatis by nonoxynol-9 in vitro. Antimicrob. Agents Chemother. 1985, 27, 724-726.
82. Bourinbaiar, A.S.; Fruhstorfer, E.C. The efficacy of nonoxynol-9 from an in vitro point of view. AIDS 1996, 10, 558-559. (Pubitemid 26138671)
83. Hicks, D.R.; Martin, L.S.; Getchell, J.P.; Heath, J.L.; Francis, D.P.; Mcdougal, J.S.; Curran, J.W.; Voeller, B. Inactivation of HTLV-III lav-infected cultures of normal human-lymphocytes by nonoxynol-9 in vitro. Lancet 1985, 2, 1422-1423.
84. Miller, C.J.; Kang, D.W.; Marthas, M.; Moldoveanu, Z.; Kiyono, H.; Marx, P.; Eldridge, J.H.; Mestecky, J.; Mcghee, J.R. Genital secretory immune-response to chronic simian immunodeficiency virus (SIV) infection: a comparison between intravenously and genitally inoculated rhesus macaques. Clin. Exp. Immunol. 1992, 88, 520-526.
85. Polsky, B.; Baron, P.A.; Gold, J.W.M.; Smith, J.L.; Jensen, R.H.; Armstrong, D. In vitro inactivation of HIV-1 by contraceptive sponge containing nonoxynol-9. Lancet 1988, 1, 1456.
86. Van Damme, L.; Ramjee, G.; Alary, M.; Vuylsteke, B.; Chandeying, V.; Rees, H.; Sirivongrangson, P.; Mukenge-Tshibaka, L.; Ettiègne- Traoré, V.; Uaheowitchai, C.; et al. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: A randomised controlled trial. Lancet 2002, 360, 971-977. (Pubitemid 35284107)
87. Schwartz, J.L.; Mauck, C.; Lai, J.J.; Creinin, M.D.; Brache, V.; Ballagh, S.A.; Weiner, D.H.; Hillier, S.L.; Fichorova, R.N.; Callahan, M. Fourteen-day safety and acceptability study of 6% cellulose sulfate gel: A randomized double-blind phase I safety study. Contraception 2006, 74, 133-140. (Pubitemid 44062469)
88. The International AIDS Society. International AIDS Society statement on announcement that two phase III trials of HIV microbicide candidate ushercell have been halted, 2007. Available online: http://www.iasociety.org/Web/ WebContent/File/Old/PDF/1263.pdf (accessed on 27 April 2012).
89. Huskens, D.; Vermeire, K.; Vandemeulebroucke, E.; Balzarini, J.; Schols, D. Safety concerns for the potential use of cyanovirin-N as microbicidal anti-HIV agent. Int. J. Biochem. Cell Biol. 2008, 40, 2802-2814.
90. Hu, Q.X.; Mahmood, N.; Shattock, R.J. High-mannose-specific deglycosylation of HIV-1 gp120 induced by resistance to cyanovirin-N and the impact on antibody neutralization. Virology 2007, 368, 145-154. (Pubitemid 47599570)
91. Huang, X.; Jin, W.; Griffin, G.E.; Shattock, R.J.; Hu, Q. Removal of two high-mannose N-linked glycans on gp120 renders human immunodeficiency virus 1 largely resistant to the carbohydrate-binding agent griffithsin. J. Gen. Virol. 2011, 92, 2367-2373.
92. Reitter, J.N.; Means, R.E.; Desrosiers, R.C. A role for carbohydrates in immune evasion in AIDS. Nat. Med. 1998, 4, 679-684. (Pubitemid 28274667)
93. Cheng-Mayer, C.; Brown A.; Harouse, J.; Luciw, P.A.; Mayer, A.J. Selection for neutralization resistance of the simian human immunodeficiency virus SHIVSF33A variant in vivo by virtue of sequence changes in the extracellular envelope glycoprotein that modify N-linked glycosylation. J. Virol. 1999, 73, 5294-5300. (Pubitemid 29274810)
94. Bolmstedt, A.; Hinkula, J.; Rowcliffe, E.; Biller, M.; Wahren, B.; Olofsson, S. Enhanced immunogenicity of a human immunodeficiency virus type 1 env DNA vaccine by manipulating N-glycosylation signals - Effects of elimination of the V3N306 glycan. Vaccine 2001, 20, 397-405. (Pubitemid 32973781)
95. Kang, S.M.; Quan, F.S.; Huang, C.Z.; Guo, L.H.; Ye, L.; Yang, C.L.; Compans, R.W. Modified HIV envelope proteins with enhanced binding to neutralizing monoclonal antibodies. Virology 2005, 331, 20-32. (Pubitemid 39593630)
96. Chackerian, B.; Rudensey, L.M.; Overbaugh, J. Specific N-linked and O-linked glycosylation modifications in the envelope V1 domain of simian immunodeficiency virus variants that evolve in the host alter recognition by neutralizing antibodies. J. Virol. 1997, 71, 7719-7727. (Pubitemid 27391717)
97. Cole, K.S.; Steckbeck, J.D.; Rowles, J.L.; Desrosiers, R.D.; Montelaro, R.C. Removal of N-linked glycosylation sites in the V1 region of simian immunodeficiency virus gp120 results in redirection of B-cell responses to V3. J. Virol. 2004, 78, 1525-1539. (Pubitemid 38095862)
98. Johnson, W.E.; Sanford, H.; Schwall, H.; Burton, D.R.; Parren, P.W.H.I.; Robinson, J.E.; Desrosiers, R.C. Assorted mutations in the envelope gene of simian immunodeficiency virus lead to loss of neutralization resistance against antibodies representing a broad spectrum of specificities. J. Virol. 2003, 77, 9993-10003. (Pubitemid 37122081)
99. Balzarini, J. Targeting the glycans of glycoproteins: A novel paradigm for antiviral therapy. Nat. Rev. Microbiol. 2007, 5, 583-597. (Pubitemid 47074114)
100. Morrow, K.; Rosen, R.; Richter, L.; Emans, A.; Forbes, A.; Day, J.; Morar, N.; Maslankowski, L.; Profy, A.T.; Kelly, C.; et al. The acceptability of an investigational vaginal microbicide, PRO 2000 gel, among women in a phase I clinical trial. J. Womens Health 2003, 12, 655-666.