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2007 AIDS Epidemic Update. December 2007. UNAIDS/WHO. http:// data.unaids.org/pub/EPISlides/2007/2007-epiupdate-en.pdf. [Accessed 20 March 2008]
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2007 AIDS Epidemic Update. December 2007. UNAIDS/WHO. http:// data.unaids.org/pub/EPISlides/2007/2007-epiupdate-en.pdf. [Accessed 20 March 2008]
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2
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33847390394
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Microbicide drug candidates to prevent HIV infection
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This comprehensive review describes the various classes of microbicides, the types of drug substances that they contain, and cellular and viral drug targets
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Balzarini J, Van Damme L. Microbicide drug candidates to prevent HIV infection. Lancet 2007; 369:787-797. This comprehensive review describes the various classes of microbicides, the types of drug substances that they contain, and cellular and viral drug targets.
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(2007)
Lancet
, vol.369
, pp. 787-797
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Balzarini, J.1
Van Damme, L.2
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3
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13844253714
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Sulfonated naphthyl porphyrins as agents against HIV-1
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Dixon DW, Gill AF, Giribabu L, et al. Sulfonated naphthyl porphyrins as agents against HIV-1. J Inorg Biochem 2005; 99:813-821.
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J Inorg Biochem
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Dixon, D.W.1
Gill, A.F.2
Giribabu, L.3
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33846135716
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Vzorov AN, Bozja J, Dixon DW, et al. Parameters of inhibition of HIV-1 infection by small anionic microbicides. Antiviral Res 2007; 73:60-68. The sulfonated porphyrins and phthalocyanines show interesting activities against a wide range of primary HIV-1 isolates and dextran sulfate-resistant viruse. Stability at vaginal pH and no activity against vaginal flora is an added feature of these compounds.
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Vzorov AN, Bozja J, Dixon DW, et al. Parameters of inhibition of HIV-1 infection by small anionic microbicides. Antiviral Res 2007; 73:60-68. The sulfonated porphyrins and phthalocyanines show interesting activities against a wide range of primary HIV-1 isolates and dextran sulfate-resistant viruse. Stability at vaginal pH and no activity against vaginal flora is an added feature of these compounds.
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5
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10344250481
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Persulfated molecular umbrellas as anti-HIV and anti-HSV agents
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Jing B, Janout V, Herold BC, et al. Persulfated molecular umbrellas as anti-HIV and anti-HSV agents. J Am Chem Soc 2004; 126:15930-15931.
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J Am Chem Soc
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Jing, B.1
Janout, V.2
Herold, B.C.3
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34447265494
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Madan RP, Mesquita PM, Cheshenko N, et al. Molecular umbrellas: a novel class of candidate topical microbicides to prevent human immunodeficiency virus and herpes simplex virus infections. J Virol 2007; 81:7636-7646. Spb8CHAS inhibits HIV and blocks HSV infection post-entry, using multiple mechanisms of action. Ability to cross membrane and target nucleus might make this compound a coitally independent agent.
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Madan RP, Mesquita PM, Cheshenko N, et al. Molecular umbrellas: a novel class of candidate topical microbicides to prevent human immunodeficiency virus and herpes simplex virus infections. J Virol 2007; 81:7636-7646. Spb8CHAS inhibits HIV and blocks HSV infection post-entry, using multiple mechanisms of action. Ability to cross membrane and target nucleus might make this compound a coitally independent agent.
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7
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34250168652
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In vitro anti-HIV and -HSV activity and safety of sodium rutin sulfate as a microbicide candidate
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A small molecule isolated from tea inhibits HIV and HSV and shows potential as microbicide DS
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Tao J, Hu Q, Yang J, et al. In vitro anti-HIV and -HSV activity and safety of sodium rutin sulfate as a microbicide candidate. Antiviral Res 2007; 75:227-233. A small molecule isolated from tea inhibits HIV and HSV and shows potential as microbicide DS.
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(2007)
Antiviral Res
, vol.75
, pp. 227-233
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Tao, J.1
Hu, Q.2
Yang, J.3
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8
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34250188089
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Synergistic inhibition of HIV-1 infection by combinations of soluble polyanions with other potential microbicides
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Gantlett KE, Weber JN, Sattentau QJ. Synergistic inhibition of HIV-1 infection by combinations of soluble polyanions with other potential microbicides. Antiviral Res 2007; 75:188-197.
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(2007)
Antiviral Res
, vol.75
, pp. 188-197
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Gantlett, K.E.1
Weber, J.N.2
Sattentau, Q.J.3
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9
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34248523190
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The future of HIV prevention: Prospects for an effective anti-HIV microbicide
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This comprehensive review provides a current look at microbicide research and development
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Nuttall J, Romano J, Douville K, et al. The future of HIV prevention: prospects for an effective anti-HIV microbicide. Infect Dis Clin North Am 2007; 21:219-239. This comprehensive review provides a current look at microbicide research and development.
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(2007)
Infect Dis Clin North Am
, vol.21
, pp. 219-239
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Nuttall, J.1
Romano, J.2
Douville, K.3
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34248370886
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Duong YT, Meadows DC, Srivastava IK, et al. Direct inactivation of human immunodeficiency virus type 1 by a novel small-molecule entry inhibitor, DCM205. Antimicrob Agents Chemother 2007; 51:1780-1786. A small molecule entry inhibitor of wide range of HIV-1 isolates disables virus particle in the absence of a cellular target.
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Duong YT, Meadows DC, Srivastava IK, et al. Direct inactivation of human immunodeficiency virus type 1 by a novel small-molecule entry inhibitor, DCM205. Antimicrob Agents Chemother 2007; 51:1780-1786. A small molecule entry inhibitor of wide range of HIV-1 isolates disables virus particle in the absence of a cellular target.
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36749087580
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Welch BD, VanDemark AP, Heroux A, et al. Potent D-peptide inhibitors of HIV-1 entry. Proc Natl Acad Sci U S A 2007; 104:16828-16833. Renewed interest in D-peptides will likely result from data presented in this paper. Proteolytic stability of D-peptides might make them useful additions to microbicide formulations
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Welch BD, VanDemark AP, Heroux A, et al. Potent D-peptide inhibitors of HIV-1 entry. Proc Natl Acad Sci U S A 2007; 104:16828-16833. Renewed interest in D-peptides will likely result from data presented in this paper. Proteolytic stability of D-peptides might make them useful additions to microbicide formulations.
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12
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37349024256
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Antimicrobial polypeptides are key anti-HIV-1 effector molecules of cervicovaginal host defense
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This brief review covers HIV-1 peptides, especially retrocyclins
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Cole AM, Cole AL. Antimicrobial polypeptides are key anti-HIV-1 effector molecules of cervicovaginal host defense. Am J Reprod Immunol 2008; 59:27-34. This brief review covers HIV-1 peptides, especially retrocyclins.
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(2008)
Am J Reprod Immunol
, vol.59
, pp. 27-34
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Cole, A.M.1
Cole, A.L.2
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Cole AL, Herasimtschuk A, Gupta P, et al. The retrocyclin analogue RC-101 prevents human immunodeficiency virus type 1 infection of a model human cervicovaginal tissue construct. Immunology 2007; 121:140-145. RC-101 remains active in an artificial vagina for an entire 9-day experiment, inducing neither tissue damage nor inflammatory cytokines. Stability and safety bodes well for a topical microbicide that contains RC-101.
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Cole AL, Herasimtschuk A, Gupta P, et al. The retrocyclin analogue RC-101 prevents human immunodeficiency virus type 1 infection of a model human cervicovaginal tissue construct. Immunology 2007; 121:140-145. RC-101 remains active in an artificial vagina for an entire 9-day experiment, inducing neither tissue damage nor inflammatory cytokines. Stability and safety bodes well for a topical microbicide that contains RC-101.
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Retrocyclin RC-101 overcomes cationic mutations on the heptad repeat 2 region of HIV-1 gp41
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Unlike many HIV-1 inhibitors, RC-101 will likely remain an active against most strains of HIV-1 that try to develop resistance to it
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Fuhrman CA, Warren AD, Waring AJ, et al. Retrocyclin RC-101 overcomes cationic mutations on the heptad repeat 2 region of HIV-1 gp41. FEBS J 2007; 274:6477-6487. Unlike many HIV-1 inhibitors, RC-101 will likely remain an active against most strains of HIV-1 that try to develop resistance to it.
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(2007)
FEBS J
, vol.274
, pp. 6477-6487
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Fuhrman, C.A.1
Warren, A.D.2
Waring, A.J.3
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0037069386
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Short constrained peptides that inhibit HIV-1 entry
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Sia SK, Carr PA, Cochran AG, et al. Short constrained peptides that inhibit HIV-1 entry. Proc Natl Acad Sci U S A 2002; 99:14664-14669.
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(2002)
Proc Natl Acad Sci U S A
, vol.99
, pp. 14664-14669
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Sia, S.K.1
Carr, P.A.2
Cochran, A.G.3
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Deng Y, Zheng Q, Ketas TJ, et al. Protein design of a bacterially expressed HIV-1 gp41 fusion inhibitor. Biochemistry 2007; 46:4360-4369. Rational design leads to a recombinant peptide that potently inhibits in-vitro infection of human T cells by a wide range of primary HIV isolates. A bacterial expression system might make C52L cost competitive.
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Deng Y, Zheng Q, Ketas TJ, et al. Protein design of a bacterially expressed HIV-1 gp41 fusion inhibitor. Biochemistry 2007; 46:4360-4369. Rational design leads to a recombinant peptide that potently inhibits in-vitro infection of human T cells by a wide range of primary HIV isolates. A bacterial expression system might make C52L cost competitive.
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34248593768
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C34, a membrane fusion inhibitor, blocks HIV infection of langerhans cells and viral transmission to T cells
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Results in skin explants indicate that C34 blocks HIV transmission when present during and after exposure to HIV. It is a candidate for combination microbicide or living microbicide
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Sugaya M, Hartley O, Root MJ, Blauvelt A. C34, a membrane fusion inhibitor, blocks HIV infection of langerhans cells and viral transmission to T cells. J Invest Dermatol 2007; 127:1436-1443. Results in skin explants indicate that C34 blocks HIV transmission when present during and after exposure to HIV. It is a candidate for combination microbicide or living microbicide.
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(2007)
J Invest Dermatol
, vol.127
, pp. 1436-1443
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Sugaya, M.1
Hartley, O.2
Root, M.J.3
Blauvelt, A.4
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Carbohydrate-binding agents (CBAs) inhibit HIV-1 infection in human primary monocyte-derived macrophages (MDMs) and efficiently prevent MDM-directed viral capture and subsequent transmission to CD4+ T lymphocytes
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This might be a useful property to have in a microbicide and to screen for
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Pollicita M, Schols D, Aquaro S, et al. Carbohydrate-binding agents (CBAs) inhibit HIV-1 infection in human primary monocyte-derived macrophages (MDMs) and efficiently prevent MDM-directed viral capture and subsequent transmission to CD4+ T lymphocytes. Virology 2008; 370:382-391. This might be a useful property to have in a microbicide and to screen for.
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(2008)
Virology
, vol.370
, pp. 382-391
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Pollicita, M.1
Schols, D.2
Aquaro, S.3
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Carbohydrate-binding agents efficiently prevent dendritic cell- specificintercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-directed HIV-1transmission to T lymphocytes
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Ability of CBAs to block DC-SIGN-mediated transmission of HIV to lymphocytes distinguishes CBAs from polyanions and other classes of entry inhibitors. This might be a useful property to have in a microbicide and to screen for
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Balzarini J, Van Herrewege Y, Vermeire K, et al. Carbohydrate-binding agents efficiently prevent dendritic cell- specificintercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-directed HIV-1transmission to T lymphocytes. Mol Pharmacol 2007; 71:3-11. Ability of CBAs to block DC-SIGN-mediated transmission of HIV to lymphocytes distinguishes CBAs from polyanions and other classes of entry inhibitors. This might be a useful property to have in a microbicide and to screen for.
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(2007)
Mol Pharmacol
, vol.71
, pp. 3-11
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Balzarini, J.1
Van Herrewege, Y.2
Vermeire, K.3
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0030790094
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Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: Potential applications to microbicide development
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Boyd MR, Gustafson KR, McMahon JB, 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.
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(1997)
Antimicrob Agents Chemother
, vol.41
, pp. 1521-1530
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Boyd, M.R.1
Gustafson, K.R.2
McMahon, J.B.3
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21
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36549005026
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PEGylation of cyanovirin-N, an entry inhibitor of HIV
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A PEGylated analog of CN-N retains in-vitro activity and might be safer and more stable in vivo
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Zappe H, Snell ME, Bossard MJ. PEGylation of cyanovirin-N, an entry inhibitor of HIV. Adv Drug Deliv Rev 2008; 60:79-87. A PEGylated analog of CN-N retains in-vitro activity and might be safer and more stable in vivo.
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(2008)
Adv Drug Deliv Rev
, vol.60
, pp. 79-87
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Zappe, H.1
Snell, M.E.2
Bossard, M.J.3
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Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti-HIV microbicide
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Emau P, Tian B, O'keefe BR, et al. Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti-HIV microbicide. J Med Primatol 2007; 36:244-253.
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(2007)
J Med Primatol
, vol.36
, pp. 244-253
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Emau, P.1
Tian, B.2
O'keefe, B.R.3
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Mannose-specific plant lectins from the Amaryllidaceae family qualify as efficient microbicides for prevention of human immunodeficiency virus infection
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Balzarini J, Hatse S, Vermeire K, et al. Mannose-specific plant lectins from the Amaryllidaceae family qualify as efficient microbicides for prevention of human immunodeficiency virus infection. Antimicrob Agents Chemother 2004; 48:3858-3870.
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(2004)
Antimicrob Agents Chemother
, vol.48
, pp. 3858-3870
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Balzarini, J.1
Hatse, S.2
Vermeire, K.3
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Differential in vitro inhibitory activity against HIV-1 of alpha-(1-3)- and alpha-(1-6)-D- mannose specific plant lectins: Implication for microbicide development
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A CBA that is active in epithelial cells and dendritic cells uses multiple mechanisms
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Saïdi H, Nasreddine N, Jenabian MA, et al. Differential in vitro inhibitory activity against HIV-1 of alpha-(1-3)- and alpha-(1-6)-D- mannose specific plant lectins: implication for microbicide development. J Transl Med 2007; 5:28. A CBA that is active in epithelial cells and dendritic cells uses multiple mechanisms.
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(2007)
J Transl Med
, vol.5
, pp. 28
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Saïdi, H.1
Nasreddine, N.2
Jenabian, M.A.3
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25
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67649983917
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Synthetic polyvalent carbohydrates as components of microbicides. World Patent Publication
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WO /033329 A1; 2007
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Wang L-X, Wang J, Fouts T. Synthetic polyvalent carbohydrates as components of microbicides. World Patent Publication WO 2007/033329 A1; 2007.
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(2007)
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Wang, L.-X.1
Wang, J.2
Fouts, T.3
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9344239350
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Medicinal chemistry applied to a synthetic protein: Development of highly potent HIV entry inhibitors
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Hartley O, Gaertner H, Wilken J, et al. Medicinal chemistry applied to a synthetic protein: development of highly potent HIV entry inhibitors. Proc Natl Acad Sci U S A 2004; 101:16460-16465.
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(2004)
Proc Natl Acad Sci U S A
, vol.101
, pp. 16460-16465
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Hartley, O.1
Gaertner, H.2
Wilken, J.3
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27
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Semisynthetic analogues of PSC-RANTES, a potent anti-HIV protein
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Semisynthetic analogs of PSC-RANTES might reduce cost of DS
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Gaertner H, Offord R, Botti P, et al. Semisynthetic analogues of PSC-RANTES, a potent anti-HIV protein. Bioconjug Chem 2008; 19:480-489. Semisynthetic analogs of PSC-RANTES might reduce cost of DS.
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(2008)
Bioconjug Chem
, vol.19
, pp. 480-489
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Gaertner, H.1
Offord, R.2
Botti, P.3
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67649993333
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Fully recombinant chemokine analogues provide complete protection in the macaque vaginal challenge model [abstract
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February, New Delhi. New Delhi: Plan it, Abstract AO21-286
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Hartley O. Fully recombinant chemokine analogues provide complete protection in the macaque vaginal challenge model [abstract]. In: Microbicides 2008; 24-27 February 2008; New Delhi. New Delhi: Plan it!; 2008. Abstract AO21-286.
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Microbicides 2008; 24-27
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Hartley, O.1
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Entry inhibitor-based microbicides are active in vitro against HIV-1 isolates from multiple genetic subtypes
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This is another example in which combinations of entry inhibitors improve efficacy of microbicides
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Ketas TJ, Schader SM, Zurita J, et al. Entry inhibitor-based microbicides are active in vitro against HIV-1 isolates from multiple genetic subtypes. Virology 2007; 364:431-440. This is another example in which combinations of entry inhibitors improve efficacy of microbicides.
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(2007)
Virology
, vol.364
, pp. 431-440
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Ketas, T.J.1
Schader, S.M.2
Zurita, J.3
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Herpes simplex virus 2 infection increases HIV acquisition in men and women: Systematic review and meta-analysis of longitudinal studies
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Freeman EE, Weiss HA, Glynn JR, et al. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS 2006; 20:73-83.
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(2006)
AIDS
, vol.20
, pp. 73-83
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Freeman, E.E.1
Weiss, H.A.2
Glynn, J.R.3
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Guzman EM, Cheshenko N, Shende V, et al. Amphipathic DNA polymers are candidate vaginal microbicides and block herpes simplex virus binding, entry and viral gene expression. Antivir Ther 2007; 12:1147-1156. Erratum in: Antivir Ther 2008; 13:335. Amphipathic DNA polymers target both HIV and HSV, acting by multiple mechanisms. A dual inhibitor might effectively reduce transmission of HIV.
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Guzman EM, Cheshenko N, Shende V, et al. Amphipathic DNA polymers are candidate vaginal microbicides and block herpes simplex virus binding, entry and viral gene expression. Antivir Ther 2007; 12:1147-1156. Erratum in: Antivir Ther 2008; 13:335. Amphipathic DNA polymers target both HIV and HSV, acting by multiple mechanisms. A dual inhibitor might effectively reduce transmission of HIV.
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Cost-effective production of a vaginal protein microbicide to prevent HIV transmission
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can expand the range of affordable microbicides. Previously discarded DSs might now be reconsidered. Production of drug substance might even take place in or near the country in which the microbicide will be used
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Ramessar K, Rademacher T, Sack M, et al. Cost-effective production of a vaginal protein microbicide to prevent HIV transmission. Proc Natl Acad Sci U S A 2008; 105:3727-3732. A general method to overcome a nagging problem (i.e. cost of drug substance) can expand the range of affordable microbicides. Previously discarded DSs might now be reconsidered. Production of drug substance might even take place in or near the country in which the microbicide will be used.
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Proc Natl Acad Sci U S A 2008; 105:3727-3732. A general method to overcome a nagging problem (i.e. cost of drug substance)
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Ramessar, K.1
Rademacher, T.2
Sack, M.3
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Development of a live topical microbicide for women [abstract
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February, New Delhi. New Delhi: Plan it, Abstract AO17-221
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Xu Q. Development of a live topical microbicide for women [abstract]. In: Microbicides 2008; 24-27 February 2008; New Delhi. New Delhi: Plan it!; 2008. Abstract AO17-221.
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Microbicides 2008; 24-27
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Xu, Q.1
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Liu JJ, Reid G, Jiang Y, et al. Activity of HIV entry and fusion inhibitors expressed by the human vaginal colonizing probiotic Lactobacillus reuteri RC-14. Cell Microbiol 2007; 9:120-130. These results demonstrate the feasibility of a powerful strategy: a living combination microbicide. HIV will be less able, or perhaps unable, to infect cells if the vagina is dosed with a constant supply of inhibitors that target three main steps of viral entry.
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Liu JJ, Reid G, Jiang Y, et al. Activity of HIV entry and fusion inhibitors expressed by the human vaginal colonizing probiotic Lactobacillus reuteri RC-14. Cell Microbiol 2007; 9:120-130. These results demonstrate the feasibility of a powerful strategy: a living combination microbicide. HIV will be less able, or perhaps unable, to infect cells if the vagina is dosed with a constant supply of inhibitors that target three main steps of viral entry.
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Vangelista L. Expression of RANTES derivatives in Lactobacilli: a novel strategy for the development of vaginal microbicides [abstract]. In: Microbicides 2008; 24-27 February 2008; New Delhi. New Delhi: Plan it!; 2008. Abstract AO18-235.
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Vangelista L. Expression of RANTES derivatives in Lactobacilli: a novel strategy for the development of vaginal microbicides [abstract]. In: Microbicides 2008; 24-27 February 2008; New Delhi. New Delhi: Plan it!; 2008. Abstract AO18-235.
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The Rockefeller Foundation Microbicide Initiative, Accessed 8 April 2008
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The Rockefeller Foundation Microbicide Initiative. The economics of microbicide development. http://www.bvgh.org/resources/market/documents/ economics.pdf. [Accessed 8 April 2008]
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The economics of microbicide development
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In vitro spermicidal and anti-HIV effects of deoxycholyltyosine
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Li W-H, Liu S-W, Ying L, et al. In vitro spermicidal and anti-HIV effects of deoxycholyltyosine. Shengzhi Yu Biyun 2007; 27:661-666.
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Shengzhi Yu Biyun
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Li, W.-H.1
Liu, S.-W.2
Ying, L.3
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40
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Inhibition of viruses by antisense oligomers capable of binding to polypurine rich tract of single-stranded RNA or RNA-DNA hybrids
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US Patent 5,849,900;
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Moelling K. Inhibition of viruses by antisense oligomers capable of binding to polypurine rich tract of single-stranded RNA or RNA-DNA hybrids. US Patent 5,849,900; 1998.
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Prevention of viral infectivity. World Patent Publication
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WO, 048644 A2; 2007. It now seems possible to induce HIV to commit suicide before it infects cells. Perhaps other classes of compounds can do the same thing
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Molling K. Prevention of viral infectivity. World Patent Publication WO 2007/ 048644 A2; 2007. It now seems possible to induce HIV to commit suicide before it infects cells. Perhaps other classes of compounds can do the same thing.
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(2007)
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Molling, K.1
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