HIV co-receptors as targets for antiviral therapy

Current Topics in Medicinal Chemistry

Volumn 4, Issue 9, 2004, Pages 883-893

  Schols, Dominique ^a  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

1 BUTYL 2,5 DIOXO 3 CYCLOHEXYLMETHYL 9 (1,4 BENZODIOXAN 6 YLMETHYL) 1,4,9 TRIAZASPIRO[5,5]UNDECANE; 1,1' [1,4 PHENYLENEBIS(METHYLENE)]BIS(1,4,8,11 TETRAAZACYCLOTETRADECANE); 2 [N METHYL N [1,3 [[4 (3 BENZYL 1 ETHYL (1H) PYRAZOL 5 YL)PIPERIDIN 1 YL]METHYL]] 4 [(3 FLUOROPHENYL)CYCLOPENT 1 YL]AMINO] 3 METHYLBUTANOIC ACID; 2 BENZHYDRYL 3 (2 METHOXYBENZYLAMINO) 1 AZABICYCLO[2.2.2]OCTANE; 4 [(4 BROMOPHENYL)(ETHOXYIMINO)METHYL] 1' [(2,4 DIMETHYL 3 PYRIDINYL)CARBONYL] 4' METHYL 1,4' BIPIPERIDINE; AMD 070; AMD 2763; ANTIRETROVIRUS AGENT; ANTIVIRUS AGENT; BETA CHEMOKINE; CHEMOKINE RECEPTOR CCR2; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CXCR4; E 913; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MACROPHAGE INFLAMMATORY PROTEIN 1BETA; MRK 1; N (6 AMINOHEXYL)GLYCYL N (3 GUANIDINOPROPYL)GLYCYL N (3 GUANIDINOPROPYL)GLYCYL N BENZYLGLYCYL N (3 GUANIDINOPROPYL)GLYCYL DEXTRO LYSYL DEXTRO LYSYL DEXTRO ARGINYL DEXTRO PROLINAMIDE; N [4 [[[6,7 DIHYDRO 2 (4 METHYLPHENYL) 5H BENZOCYCLOHEPTEN 8 YL]CARBONYL]AMINO]BENZYL] N,N DIMETHYL 2H TETRAHYDROPYRAN 4 AMINIUM CHLORIDE; N ALPHA ACETYL NONA DEXTRO AMIDE ACETATE; NELFINAVIR; POLYPHEMUSIN[5,12 TYROSINE 7 LYSINE]; RANTES; RITONAVIR; STROMAL CELL DERIVED FACTOR 1; T 134; T 22; TRANSACTIVATOR PROTEIN; UNCLASSIFIED DRUG; ZIDOVUDINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; LIGAND;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; CLINICAL TRIAL; DRUG ABSORPTION; DRUG HALF LIFE; DRUG INFUSION; DRUG POTENTIATION; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG TARGETING; DRUG TOLERABILITY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; MACROPHAGE; MOLECULAR WEIGHT; NONHUMAN; REVIEW; SIDE EFFECT; STRUCTURE ANALYSIS; T LYMPHOCYTE; VIRUS LOAD; VIRUS REPLICATION; VIRUS STRAIN; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; METABOLISM; PHYSIOLOGY; VIROLOGY;

ANIMALS; ANTI-HIV AGENTS; HIV INFECTIONS; HIV-1; HUMANS; LIGANDS; MOLECULAR STRUCTURE; RECEPTORS, CCR5; RECEPTORS, CXCR4; VIRUS REPLICATION;

EID: 2942555662     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/1568026043388501     Document Type: Review

References (115)

1. Feng, Y., Broder, C.C., Kennedy, P.E., Berger, E.A. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 1996, 272, 872-877.
2. Bleul, C.C., Farzan, M., Choe, H., Parolin, C., Clark-Lewis, I., Sodroski, J., Springer, T.A. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 1996, 382, 829-832.
3. Oberlin, E., Amara, A., Bachelerie, F., Bessia, C., Virelizier, J.L., Arenzana-Seisdedos, F., Schwartz, O., Heard, J.M., Clark-Lewis, I., Legler, D.F., Loetscher, M., Bagggiolini, M., Moser, B. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 1996, 382, 833-835.
4. Tashiro, K., Tada, H., Heilker, R., Shirozu, M., Nakano, T., Honjo, T. Signal sequence trap: a cloning strategy for secreted proteins and type 1 membrane proteins. Science 1993, 261, 600-603.
5. + T cells. Science 1995, 270, 1811-1815.
6. Combadière, C., Ahuja, S.K., Tiffany, H.L., Murphy, P.M. Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1α, MIP-1β, and RANTES. Journal of Leukocyte Biology 1996, 60, 147-152
7. Samson, M., Labbe, O., Mollereau, C., Vassart, G., Parmentier, M. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry 1996, 35, 3362-3367.
8. Raport, C.J., Gosling, J., Schweickart, V.L., Gray, P.W., Charo, I.F. Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1β, and MIP-1α. Journal of Biological Chemistry 1996, 271, 17161-17166.
9. Deng, H., Liu, R., Ellmeier, W., Choe, S., Unutmaz, D., Burkhart, M., Marzio, P.D., Marmon, S., Sutton, R.E., Hill, C.M., Davis, C.B., Peiper, S.C., Schall, T.J., Littman, D.R., Landau, R. Identification of a major co-receptor for primary isolates of HIV-1. Nature 1996, 381,661-666.
10. + cells is mediated by the chemokine receptor CC-CKR-5. Nature 1996, 381, 667-673.
11. Alkhatib, G., Combadière, C., Broder, C.C., Feng, Y., Kennedy, P.E., Murphy, P.M., Berger, E.A. CC CKR5: a RANTES, MIP-1α , MIP-1β receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 1996, 272, 1955-1958.
12. Choe, H., Farzan, M., Sun, Y., Sullivan, N., Rollins, B., Ponath, P.D., Wu, L., Mackay, C.R., LaRosa, G., Newman, W., Gerard, N., Gerard, C., Sodroski, J. The β-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 1996, 85, 1135-1148.
13. Doranz, B.J., Rucker, J., Yi, Y., Smyth, R.J., Samson, M., Peiper, S.C., Parmentier, M., Collman, R.G., Doms, R.W. A dual-tropic primary HIV-1 isolate that uses fusin and the β-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 1996, 85, 1149-1158.
14. Berger, E.A., Doms, R.W., Fenyo, E.M., Korber, B.T., Littman, D.R., Moore, J.P., Sattentau, Q.J., Schuitemaker, H., Sodroski, J., Weiss, R.A. A new classification for HIV-1. Nature 1998, 391, 240.
15. Dean, M., Carrington, M., Winkler, C., Huttley, G.A., Smith, M.W., Allikmets, R., Goedert, J.J., Buchbinder, S.P., Vittinghoff, E., Gomperts, E., Donfield, S., Vlahov, D., Kaslow, R., Saah, A., Rinaldo, C., Detels, R. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study, O'Brien SJ. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 1996, 273, 1856-1862.
16. Huang, Y., W. A. Paxton, S. M. Wolinsky, A. U. Neumann, L. Zhang, T. He, S. Kang, D. Ceradini, Z. Jin, K. Yazdanbakhsh, K. Kunstman, D. Erickson, E. Dragon, N. R. Landau, J. Phair, D. D. Ho, R. A. Koup. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat. Med. 1996, 2, 1240-1243.
17. Liu, R., Paxton, W.A., Choe, S., Ceradini, D., Martin, S.R., Horuk, R., MacDonald, M.E., Stuhlmann, H., Koup, R.A., Landau, N.R. Homozygous defect in HIV-1 co-receptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 1996, 86, 367-377.
18. Samson, M., Libert, F., Doranz, B.J., Rucker, J., Liesnard, C., Farber, C.-M., Saragosti, S., Lapouméroulie, C., Cognaux, J., Forceille, C., Muyldermans, G., Verhofstede, C., Burtonboy, G., Georges, M., Imai, T., Rana, S., Yi, Y., Smyth, R.J., Collman, R.G., Doms, R.W., Vassart, G., Parmentier, M. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 1996, 382, 722-725.
19. Cocchi, F., DeVico, A.L., Yarchoan, R., Redfield, R., Cleghorn, F., Blattner, W.A., Garzino-Demo, A., Colombini-Hatch, S., Margolis, D., Gallo, R.C. Higher macrophage inflammatory protein (MIP)-1α and MIP-1β levels from CD8+ T cells are associated with asymptomatic HIV-1 infection. Proc. Natl. Acad. Sci. USA 2000, 97, 13812-13817.
20. Paxton, W.A., Martin, S.R., Tse, D., O'Brien, T.R., Skurnick, J., VanDevanter, N.L., Padian, N., Braun, J.F., Kotler, D.P., Wolinsky, S.M., Koup, R.A. Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposure. Nature Medicine 1996, 2, 412-417
21. Paxton, W.A., Neumann, A.U., Kang, S., Deutch, L., Brown, R.C., Koup, R.A., Wolinsky, S.M. RANTES production from CD4+ lymphocytes correlates with host genotype and rates of human immunodeficiency virus type 1 disease progression. J. Infect Dis. 2001, 183, 1678-1681.
22. Zagury, D., Lachgar, A., Chams, V., Fall, L.S., Bernard, J., Zagury, J.F., Bizzini, B., Gringeri, A., Santagostino, E., Rappaport, J., Feldman, M., O'Brien, S.J., Burny, A., Gallo, R.C. C-C chemokines, pivotal in protection against HIV type 1 infection. Proceedings of the National Academy of Sciences, USA 1998, 95, 3857-3861.
23. Derdeyn, C.A., Costello, C., Kilby, J.M., Sfakianos, G., Saag, M.S., Kaslow, R., Bucy, R.P. Correlation between circulating stromal cell-derived factor 1 levels and CD4+ cell count in human immunodeficiency virus type 1-infected individuals. AIDS Res. Hum Retroviruses 1999, 15, 1063-1071.
24. Soriano, A., Martinez, C., Garcia, F., Plana, M., Palou, E., Lejeune, M., Arostegui, J.I., De Lazzari, E., Rodriguez, C., Barrasa, A., Lorenzo, J.I., Alcami, J., del Romero, J., Miro, J.M., Gatell, J.M., Gallart, T. Plasma stromal cell-derived factor (SDF)-1 levels, SDF1-3′A genotype, and expression of CXCR4 on T lymphocytes: their impact on resistance to human immunodeficiency virus type 1 infection and its progression. J. Infect. Dis. 2002, 186, 922-931.
25. Zlotnik, A., Yoshie, O. Chemokines: a new classification system and their role in immunity. Immunity 2000, 12, 121-127.
26. Cocchi, F., DeVico, A.L., Garzino-Demo, A., Cara, A., Gallo, R.C., Lusso, P. The V3 domain of the HIV-1 gp120 envelope glycoprotein is critical for chemokine-mediated blockade of infection. Nature Medicine 1996, 2, 1244-1247.
27. Schmidtmayerova, H., Sherry, B., Bukrinsky, M. Chemokines and HIV replication. Nature 1996, 382, 767.
28. Dolei, A., Biolchini, A., Serra, C., Curreli, S., Gomes, E., Dianzani, F. Increased replication of T-cell-tropic HIV strains and CXC-chemokine receptor-4 induction in T cells treated with macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES beta-chemokines. AIDS 1998, 12, 183-190.
29. Kelly, M.D., Naif, H.M., Adams, S.L., Cunningham, A.L., Lloyd, A.R. Dichotomous effects of beta-chemokines on HIV replication in monocytes and monocyte-derived macrophages. Journal of Immunology 1998, 160, 3091-3095.
30. Gordon, C.J., Muesing, M.A., Proudfoot, A.E.I., Power, C.A., Moore, J.P. & Trkola, A. Enhancement of human immunodeficiency virus type 1 infection by the CC-chemokine RANTES is independent of the mechanism of virus-cell fusion. Journal of Virology 1999, 73, 684-694.
31. Kinter, A., Catanzaro, A., Monaco, J., Ruiz, M., Justement, J., Moir, S., Arthos, J., Oliva, A., Ehler, L., Mizell, S., Jackson, R., Ostrowski, M., Hoxie, J., Offord, R., Fauci, A.S. CC-chemokines enhance the replication of T-tropic strains of HIV-1 in CD4(+) T cells: role of signal transduction. Proceedings of the National Academy of Sciences USA 1998, 95, 11880-11885.
32. Maréchal, V., Arenzana-Seisdedos, F., Heard, M., Schwartz, O. Opposite effects of SDF-1 on human immunodeficiency virus type 1 replication. Journal of Virology 1999, 73:3608-3615.
33. Simmons, G., Clapham, P.R., Picard, L., Offord, R.E., Rosenkilde, M.M., Schwartz, T.W., Buser, R., Wells, T.N.C., Proudfoot, A.E.I. Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist. Science 1997, 276,276-279.
34. Arenzana-Seisdedos, F., Virelizier, J.L., Rousset, D., Clark-Lewis, I., Loetscher, P., Moser, B., Baggiolini, M. HIV blocked by chemokine antagonist. Nature 1996, 383:400.
35. Ylisastigui, L., Vizzavona, J., Drakopoulou, E., Paindavoine, P., Calvo, C.-F., Parmentier, M., Gluckman, J.C., Vita, C., Benjouad, A. Synthetic full-length and truncated RANTES inhibit HIV-1 infection of primary macrophages. AIDS 1998, 12, 977-984.
36. Torre, V.S., Marozsan, A.J., Albright, J.L., Collins, K.R., Hartley, O., Offord, R.E., Quinones-Mateu, M.E., Arts, E.J. Protein variable sensitivity of CCR5-tropic human immunodeficiency virus type 1 isolates to inhibition by RANTES analogs. J. Virol. 2000, 74, 4868-4876.
37. Elsner, J., Dulkys, Y., Kimmig, D., Wells, T.N., Proudfoot, A.E., Kapp, A. Aminooxypentane-RANTES induces CCR3 activation and internalization of CCR3 from the surface of human eosinophils. Int Arch Allergy Immunol. 2001, 124, 227-9.
38. Polo, S., Nardese, V., De Santis, C., Arcelloni, C., Paroni, R., Sironi, F., Verani, A., Rizzi, M., Bolognesi, M., Lusso, P. Enhancement of the HIV-1 inhibitory activity of RANTES by modification of the N-terminal region: dissociation from CCR5 activation. Eur J Immunol. 2000, 30, 3190-3198.
39. Yang, O.O., Swanberg, S.L., Lu, Z., Dziejman, M., McCoy, J., Luster, A.D., Walker, B.D., Herrmann, S.H. Enhanced inhibition of human immunodeficiency virus type 1 by Met-stromal-derived factor 1β correlates with down-modulation of CXCR4. Journal of Virology 1999, 73, 4582-4589.
40. Rusconi, S., La Seta, Catamancio, S., Citterio, P., Bulgheroni, E., Croce, F., Herrmann, S.H., Offord, R.E., Galli, M., Hirsch, M.S. Combination of CCR5 and CXCR4 inhibitors in therapy of human immunodeficiency virus type 1 infection: in vitro studies of mixed virus infections. J. Virol. 2000, 74, 9328-32.
41. Menten, P., Struyf, S., Schutyser, E., De Clercq, E., Schols, D., Proost, P., Van Damme, J. The LD78β isoform of MIP-1α is the most potent CCR5 agonist and HIV-1- inhibiting chemokine. Journal of Clinical Investigation 1999, 104:R1-R5.
42. Nibbs, R.J., Yang, J., Landau, N.R., Mao, J.H., Graham, G.J. LD78β, a non-allelic variant of human MIP-1α (LD78α), has enhanced receptor interactions and potent HIV suppressive activity. Journal of Biological Chemistry 1999, 274: 17478-17483.
43. Xin, X., Shioda, T., Kato, A., Liu, H., Sakai, Y., Nagai, Y.. Enhanced anti-HIV-1 activity of CC-chemokine LD78 β a non-allelic variant of MIP-1α/LD78α. FEBS Letters 1999, 457:219-222.
44. Aquaro, S., Menten, P., Struyf, S., Proost, P., Van Damme, J., De Clercq, E., Schols, D. The LD78β isoform of MIP-1α is the most potent CC-chemokine in inhibiting CCR5-dependent human immuno-deficiency virus type 1 replication in human macrophages. J. Virol. 2001, 75, 4402-4406.
45. Townson, J.R., Graham, G.J., Landau, N.R., Rasala, B., Nibbs, R.J.. Aminooxypentane addition to the chemokine macrophage inflammatory protein-1alpha P increases receptor affinities and HIV inhibition. J. Biol. Chem. 2000, 275, 39254-39261.
46. Amara, A., Gall, S.L., Schwartz, O., Salamero, J., Montes, M., Loetscher, P., Baggiolini, M., Virelizier, J.L., Arenzana-Seisdedos, F. HIV coreceptor downregulation as antiviral principle: SDF-1α-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication. Journal of Experimental Medicine 1997, 186, 139-146.
47. Mosier, D.E., Picchio, G.R., Gulizia, R.J., Sabbe, R., Poignard, P., Picard, L., Offord, R.E., Thompson, D.A., Wilken, J. Highly potent RANTES analogues either prevent CCR5-using human immunodeficiency virus type 1 infection in vivo or rapidly select for CXCR4-using variants. Journal of Virology 1999, 73, 3544-3550.
48. Kledal, T.N., Rosenkilde, M.M., Coulin, F., Simmons, G., Johnsen, A.H., Alouani, S., Power, C.A., Luttichau, H.R., Gerstoft, J., Clapham, P.R., Clark-Lewis, I., Wells, T.N.C., Schwartz, T.W. A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus. Science 1997, 277, 1656-1659.
49. Zhou, N., Luo, Z., Luo, J., Hall, J.W., Huang, Z. A novel peptide antagonist of CXCR4 derived from the N-terminus of viral chemokine vMIP-II. Biochemistry 2000, 39, 3782-3787.
50. Baba, M., Nishimura, O., Kanzaki, N., Okamoto, M., Sawada, H., Iizawa, Y., Shiraishi, M., Aramaki, Y., Okonogi, K., Ogawa, Y., Meguro, K., Fujino, M. A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc. Natl. Acad. Sci. USA 1999, 96, 5698-703.
51. Dragic, T., Trkola, A., Thompson, D.A., Cormier, E.G., Kajumo, F.A., Maxwell, E., Lin, S.W., Ying, W., Smith, S.O., Sakmar, T.P., Moore, J.P. A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proceedings of the National Academy of Sciences, USA 2000, 97, 5639-5644.
52. Gao, P., Zhou, X.Y., Yashiro-Ohtani, Y., Yang, Y.F., Sugimoto, N., Ono, S., Nakanishi, T., Obika, S., Imanishi, T., Egawa, T., Nagasawa, T., Fujiwara, H., Hamaoka, T. The unique target specificity of a nonpeptide chemokine receptor antagonist: selective blockade of two Th1 chemokine receptors CCR5 and CXCR3. J. Leukocyte Biol. 2003, 73, 273-280.
53. Palani, A., Shapiro, S., Clader, J.W., Greenlee, W.J., Cox, K., Strizki, J., Endres, M., Baroudy, B.M. Discovery of 4-[(Z)-(4-bromophenyl)- (ethoxyimino)methyl]-1′-[(2,4-dimethyl-3-pyridinyl) carbonyl]-4′-methyl-1,4′- bipiperidine N-oxide (SCH 351125): an orally bioavailable human CCR5 antagonist for the treatment of HIV infection. J. Med. Chem. 2001, 44, 3339-3342.
54. Strizki, J.M., Xu, S., Wagner, N.E., Wojcik, L., Liu, J., Hou, Y., Endres, M., Palani, A., Shapiro, S., Clader, J.W., Greenlee, W.J., Tagat, J.R., McCombie, S., Cox, K., Fawzi, A.B., Chou, C.C., Pugliese-Sivo, C., Davies, L., Moreno, M.E., Ho, D.D., Trkola, A., Stoddart, C.A., Moore, J.P., Reyes, G.R., Baroudy, B.M. SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proc. Natl. Acad. Sci. USA 2001, 98, 12718-12723.
55. Reynes, J., Rouzier, R., Kanouni, T., Baillat, V., Baroudy, B., Keung, A., Hogan, C., Markowitz, M., Laughlin, M. SCH C: Safety and antiviral effects of a CCR5 receptor antagonist in HIV-1 infected subjects. From: 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, WA, USA. Abstractbook, abstract #1, p.53.
56. Maeda, K., Yoshimura, K., Shibayama, S., Habashita, H., Tada, H., Sagawa, K., Miyakawa, T., Aoki, M., Fukushima, D., Mitsuya, H. Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5. J. Biol. Chem. 2001, 276, 35194-35200.
57. Kumar, S., Kwei, G.Y., Poon, G.K., Iliff, S.A., Wang, Y., Chen, Q., Franklin, R.B., Didolkar, V., Wang, R.W., Yamazaki, M., Chiu, S.H., Lin, J.H., Pearson, P.G., Baillie, T.A. Pharmacokinetics and interactions of a novel antagonist of chemokine receptor 5 (CCR5) with ritonavir in rats and monkeys: role of CYP3A and P-glycoprotein. J. Pharmacol. Exp. Ther. 2003, 304, 1161-1171.
58. Lai, J.P., Ho, W.Z., Zhan, G.X., Yi, Y., Coltman, R.G., Douglas, S.D. Substance P antagonist (CP-96,345) inhibits HIV-1 replication in human mononuclear phagocytes. Proc. Natl. Acad. Sci. USA 2001, 98, 3970-3975.
59. 7]-polyphemusin II). Biochemical and Biophysical Research Communications 1992, 189, 845-850.
60. Nakashima, H., Masuda, M., Murakami, T., Koyanagi, Y., Matsumoto, A., Fujii, N., Yamamoto, N. Anti-human immunodeficiency virus activity of a novel synthetic peptide, T22 ([Tyr-5,12, Lys-7]polyphemusin II): a possible inhibitor of virus-cell fusion. Antimicrobial Agents and Chemotherapy 1992, 36, 1249-1255.
61. Murakami, T., Nakajima, T., Koyanagi, Y., Tachibana, K., Fujii, N., Tamamura, H., Yoshida, N., Waki, M., Matsumoto, A., Yoshie, O., Kishimoto, T., Yamamoto, N. & Nagasawa, T. A small molecule CXCR4 inhibitor that blocks T cell line-tropic HIV-1 infection. Journal of Experimental Medicine 1997, 186, 1389-1393.
62. Arakaki, R., Tamamura, H., Premanathan, M., Kanbara, K., Ramanan, S., Mochizuki, K., Baba, M., Fujii, N., Nakashima, H. T134, a small-molecule CXCR4 inhibitor, has no cross-drug resistance with AMD3100, a CXCR4 antagonist with a different structure. Journal of Virology 1999, 73, 1719-1723.
63. Sumner-Smith, M., Zheng, Y., Zhang, Y.P., Twist, E.M., Climie, S.C. Antiherpetic activities of N-α-acetyl-nona-D-arginine amide acetate. Drugs under Experimental and Clinical Research 1995, 21, 1-6.
64. O'Brien, W.A., Sumner-Smith, M., Mao, S.-H., Sadeghi, S., Zhao, J.-Q. & Chen, I.S.Y. Anti-human immunodeficiency virus type 1 activity of an oligocationic compound mediated via gp120 V3 interactions. Journal of Virology 1996, 70:2825-2831.
65. Doranz, B.J., Grovit-Ferbas, K., Sharron, M.P., Mao, S.-H., Goetz, M.B., Daar, E.S., Doms, R.W., O'Brien, W.A. A small-molecule inhibitor directed against the chemokine receptor CXCR4 prevents its use as an HIV-1 coreceptor. Journal of Experimental Medicine 1997, 186, 1395-1400.
66. Doranz, B.J., Filion, L.G., Diaz-Mitoma, F., Sitar, D.S., Sahai, J., Baribaud, F., Orsini, M.J., Benovic, J.L., Cameron, W., Doms, R.W. Safe use of the CXCR4 inhibitor ALX40-4C in humans. AIDS Res Hum Retroviruses. 2001, 17, 475-486.
67. Xiao, H., Neuveut, C., Tiffany, H.L., Benkirane, M., Rich, E.A., Murphy, P.M., Jeang, K.-T. Selective CXCR4 antagonism by tat: implications for in vivo expansion of coreceptor use by HIV-1. Proceedings of the National Academy of Sciences, USA 2000, 97, 11466-11471.
68. Ghezzi, S., Noonam, D.M., Aluigi M.G., Vallanti G., Cota M., Benelli R., Morini M., Reeves J.D., Vicenzi E., Poli G. Albini A. Inhibition of CXCR4-dependent HIV-1 infection by extracellular HIV-1 Tat. Biochem Biophys Res Commun. 2000, 270, 992-996.
69. Kashanchi, F., Sadaie, M.R., Brady, J.N. Inhibition of HIV-1 transcription and virus replication using soluble Tat peptide analogs. Virology 1997, 227:431-438.
70. Choudhury, I., Wang, J., Rabson, A.B., Stein, S., Pooyan, S., Stein, S., Leibowitz, M.J. Inhibition of HIV-1 replication by a Tat RNA-binding domain peptide analog. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 1998, 17:104-111.
71. Hamy, F., Felder, E.R., Heizmann, G., Lazdins, J., Aboul-Ela, F., Varani, G., Karn, J., Klimkait, T. An inhibitor of the Tat/TAR RNA interaction that effectively suppresses HIV-1 replication. Proceedings of the National Academy of Sciences, USA 1997, 94,3548-3553.
72. Daelemans, D., Schols, D., Witvrouw, M., Pannecouque, C., Hatse, S., Van Dooren, S., Hamy, I., Klimkait, T., De Clercq, E. & Vandamme, A.-M. A second target for the peptoid Tat/transactivation response element inhibitor CGP64222: inhibition of human immunodeficiency virus replication by blocking CXC-chemokine receptor 4-mediated virus entry. Molecular Pharmacology 2000, 57:116-124.
73. De Clercq, E., Yamamoto, N., Pauwels, R., Baba, M., Schols, D., Nakashima, H., Balzarini, J., Debyser, Z., Murrer, B.A., Schwartz, D., Thornton, D., Bridger, G., Fricker, S., Henson, G., Abrams, M., Picker, D. Potent and selective inhibition of human immunodeficiency virus (HIV)-1 and HIV-2 replication by a class of bicyclams interacting with a viral uncoating event. Proceedings of the National Academy of Sciences, USA 1992, 89,5286-5290.
74. De Clercq, E., Yamamoto, N., Pauwels, R., Balzarini, J., Witvrouw, M., De Vreese, K., Debyser, Z., Rosenwirth, B., Peichl, P., Datema, R., Thornton, D., Skerlj, R., Gaul, F., Padmanabhan, S., Bridger, G., Henson, G., Abrams, M. Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivative JM3100. Antimicrobial Agents and Chemotherapy 1994, 38, 668-674.
75. Bridget, G.J., Skerlj, R.T., Thornton, D., Padmanabhan, S., Martellucci, S.A., Henson, G.W., Abrams, M.J., Yamamoto, N., De Vreese, K., Pauwels, R., De Clercq, E. Synthesis and structure-activity relationships of phenylenebis(methylene)linked bis-tetraazamacrocycles that inhibit HIV replication. Effects of macrocyclic ring size and substituents on the aromatic linker. Journal of Medicinal Chemistry 1995, 38:366-378.
76. Bridger, G.J., Skerlj, R.T., Padmanabhan, S., Martellucci, S.A., Henson, G.W., Abrams, M.J., Joao, H., Witvrouw, M., De Vreese, K., Pauwels, R., De Clercq, E. Synthesis and structure-activity relationships of phenylenebis(methylene) linked bis-tetraazamacrocycles that inhibit HIV replication. 2. Effect of heteroaromatic linkers on the activity of bicyclams. J. Med. Chem. 1996, 39:109-119.
77. Joao HC, De Vreese K, Pauwels R, De Clercq E, Henson GW & Bridger GJ. Quantitative structural activity relationship study of bis-tetraazacyclic compounds - a novel series of HIV-1 and HIV-2 inhibitors. Journal of Medicinal Chemistry 1995, 38:3865-3873.
78. Schols D, Struyf S, Van Damme J, Esté JA, Henson G, De Clereq E. Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4. Journal of Experimental Medicine 1997, 186, 1383-1388.
79. Schols, D., Esté, J.A,, Henson, G., De Clercq, E. Bicyclams, a class of potent anti-HIV agents, are targeted at the HIV coreceptor fusin/CXCR-4. Antiviral Research 1997, 35, 147-156.
80. Donzella, G.A., Schols, D., Lin, S.W., Esté, J.A., Nagashima, K.A., Maddon, P.J., Allaway, G.P., Sakmar, T.P., Henson, G., De Clercq, E., Moore, J.P. AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nature Medicine 1998, 4, 72-77.
81. Esté, J.A., Cabrera, C., De Clercq, E., Struyf, S., Van Damme, J., Bridger, G., Skerlj, R.T., Abrams, M.J., Henson, G., Gutierrez, A., Clotet, B., Schols, D. Activity of different bicyclam derivatives against human immunodeficiency virus depends on their interaction with the CXCR4 chemokine receptor. Molecular Pharmacology 1999, 55, 67-73.
82. Bridger, G.J., Skerlj, R.T., Padmanabhan, S., Martellucci, S.A., Henson, G.W., Struyf, S., Witvrouw, M., Schols, D., De Clercq, E. Synthesis and structure-activity relationships of phenylenebis (methylene)-linked bis-azamacrocycles that inhibit HIV-1 and HIV-2 replication by antagonism of the chemokine receptor CXCR4. J. Med. Chem. 1999, 42, 3971-3981.
83. Simmons, G., Reeves, J.D., McKnight, A., Dejucq, N., Hibbitts, S, Power CA, Aarons E, Schols D, De Clercq E, Proudfoot AE & Clapham PR. CXCR4 as a functional coreceptor for human immunodeficiency virus type 1 infection of primary macrophages. Journal of Virology 1998, 72:8453-8457.
84. Yi, Y., Isaacs, S.N., Williams, D.A., Frank, I., Schols, D., De Clercq, E., Kolson, D.L., Collman, R.G. Role of CXCR4 in cell-cell fusion and infection of monocyte-derived macrophages by primary human immunodeficiency virus type 1 (HIV-1) strains: two distinct mechanisms of HIV-1 dual tropism. Journal of Virology 1999, 73:7117-7125.
85. De Clercq, E. Inhibition of HIV infection by bicyclams, highly potent and specific CXCR4 antagonists. Molecular Pharmacology 2000, 57, 833-839.
86. Hatse S, Princen K, Bridger G, De Clercq E, Schols D. Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4. FEBS Lett. 2002, 527, 255-262.
87. Esté, J.A., Cabrera, C., Blanco, J., Gutierrez, A., Bridger, G., Henson, G., Clotet, B., Schols, D., De Clercq, E. Shift of clinical human immunodeficiency virus type 1 isolates from X4 to R5 and prevention of emergence of the syncytium-inducing phenotype by blockade of CXCR4. Journal of Virology 1999, 73, 5577-5585.
88. Schols, D., Fonteyn, E., Bridger, G., Henson, G., De Clercq, E. The CXCR4 receptor antagonist, AMD3100, strongly inhibits HIV infection in SCID-hu PBMC mice. The 39th Interscience Conference on Antimicrobial Agents and Chemotherapy Meeting, San Francisco, California, September 25-29, 1999. Abstract book, abstract no. 915, p. 313.
89. Datema, R., Rabin, L., Hincenberghs, M., Moreno, M.B., Warren, S., Linquist, V., Rosenwirth, B., Seifert, J., McCune, J.M. Antiviral efficacy in vivo of the anti-human immunodeficiency virus bicyclam SDZ SID 791 (JM3100), an inhibitor of infectious cell entry. Antimicrobial Agents and Chemotherapy 1996, 40, 750-754.
90. Gorry, P.R., Bristol, G., Zack, J.A., Ritola, K., Swanstrom, R., Birch, C.J., Bell, J.E., Bannert, N., Crawford, K., Wang, H., Schols, D., De Clercq, E., Kunstman, K., Wolinsky, S.M., Gabuzda, D. Macrophage tropism of human immunodeficiency virus type 1 isolates from brain and lymphoid tissues predicts neurotropism independent of coreceptor specificity. J. Virol. 2001, 75, 10073-10089.
91. Koning, F.A., Schols, D., Schuitemaker, H. No selection for CCR5 coreceptor usage during parenteral transmission of macrophagetropic syncytium-inducing human immunodeficiency virus type 1. J. Virol. 2001, 75, 8848-9853.
92. Naif, H.M., Cunningham, A.L., Alali, M., Li, S., Nasr, N., Buhler, M.M., Schols, D., De Clercq, E., Stewart, G. A human immunodeficiency virus type 1 isolate from an infected person homozygous for CCR5Delta32 exhibits dual tropism by infecting macrophages and MT2 cells via CXCR4. J. Virol. 2002, 76, 3114-3124.
93. Connor, R.I., Sheridan, K.E., Ceradini, D., Choe, S., Landau, N.R. Change in coreceptor use correlates with disease progression in HIV-1 infected individuals. Journal of Experimental Medicine 1997, 185, 621-628.
94. Scarlatti, G., Tresoldi, E., Bjorndal, A., Fredriksson, R., Colognesi, C., Deng, H.K., Malnati, M.S., Plebani, A., Siccardi, A.G., Littman, D.R., Fenyo, E.M., Lasso, P. In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression. Nature Medicine 1997, 3, 1259-1265.
95. Labrosse, B., Brelot, A., Heveker, N., Sol, N., Schols, D., De Clercq, E., Alizon, M. Determinants for sensitivity of human immunodeficiency virus coreceptor CXCR4 to the bicyclam AMD3100. Journal of Virology 1998, 72, 6381-76388.
96. Gerlach, L. O., Skerlj, R. T., Bridger, G. J., Schwartz. T. W. Molecular interactions of cyclam and bicyclam non-peptide antagonists with the CXCR4 chemokine receptor. J. Biol. Chem. 2001, 276, 14153-14160.
97. Hatse, S., Princen, K., Gerlach, L.O., Bridger, G,, Henson, G, De Clercq, E., Schwartz, T.W., Schols, D. Mutation of Asp(171) and Asp(262) of the chemokine receptor CXCR4 impairs its coreceptor function for human immunodeficiency virus-1 entry and abrogates the antagonistic activity of AMD3100. Mol. Pharmacol. 2001, 60, 164-173.
98. De Vreese, K., Reymen, D., Griffin, P., Steinkasserer, A., Werner, G., Bridger, G.J., Esté, J., James, W., Henson, G.W., Desmyter, J., Anné, J., De Clercq, E. The bicyclams, a new class of potent human immunodeficiency virus inhibitors, block viral entry after binding. Antiviral Research 1996, 29, 209-219.
99. De Vreese, K., Kofler-Mongold, V., Leutgeb, C., Weber, V., Vermeire, K., Schacht, S., Anné, J., De Clercq, E., Datema, R., Werner, G. The molecular target of bicyclams, potent inhibitors of human immunodeficiency virus replication. Journal of Virology 1996, 70, 689-696.
100. De Vreese, K., Van Nerum, I., Vermeire, K., Anné, J., De Clercq, E. Sensitivity of human immunodeficiency virus to bicyclam derivatives is influenced by the three-dimensional structure of gp120. Antimicrobial Agents and Chemotherapy 1997, 41, 2616-2120.
101. Schols, D., Esté Cabrera, C., De Clercq, E. T-Cell-line-tropic human immunodeficiency virus type 1 that is made resistant to stromal cell-derived factor 1α contains mutations in the envelope gp120 but does not show a switch in coreceptor use. Journal of Virology 1998, 72, 4032-4037.
102. Trkola, A., Kuhmann, S.E., Strizki, J.M., Maxwell, E., Ketas, T., Morgan, T., Pugach, P., Xu, S., Wojcik, L., Tagat, J., Palani, A., Shapiro, S., Clader, J.W., McCombie, S., Reyes, G.R., Baroudy, B.M., Moore, J.P. HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. Proc. Natl. Acad. Sci. USA 2002, 99, 395-400.
103. Glushakova, S., Yi, Y., Grivel, J.-C., Singh, A., Schols, D., De Clercq, E., Collman, R.G., Margolis, L. Preferential coreceptor utilization and cytopathicity by dual-tropic HIV-1 in human lymphoid tissue ex vivo. Journal of Clinical Investigation 1999, 104:R7-R11.
104. Schramm, B., Penn, M.L., Speck, R.F., Chan, S.Y., De Clercq, E., Schols, D., Connor, R.I. & Goldsmith, M.A. (2000) Viral entry through CXCR4 is a pathogenic factor and therapeutic target in human immunodeficiency virus type 1 disease. 2000. Journal of Virology 2000, 74, 184-192.
105. Malkevitch, N., McDermott, D.H., Yi, Y., Grivel, J.C., Schols, D., De Clercq, E., Murphy, P.M., Glushakova, S., Collman, R.G., Margolis, L. Coreceptor choice and T cell depletion by R5, X4, and R5X4 HIV-1 variants in CCR5-deficient (CCR5delta32) and normal human lymphoid tissue. Virology. 2001, 281, 239-47.
106. Hendrix, C.W., Flexner, C., MacFarland, R.T., Giandomenico, C., Fuchs, E.J., Redpath, F., Bridger, G., Henson, G.W. Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers. Antimicrobial Agents and Chemotherapy 2000, 44:1667-1673.
107. Schols, D., Claes, S., De Clercq, E., Hendrix, C., Bridger, G., Calandra, G., Henson, G.W., Fransen, S., Huang, W., Whitcomb, J.M., Petropoulos, C.J. and AMD-3100 HIV study group. AMD-3100, a CXCR4 antagonist, reduced HIV viral load and X4 virus levels in humans. 9th Conference on Retroviruses and Opportunistic Infections, Seattle, USA, February 24-28, 2002. Abstractbook, abstract #2, p.53.
108. Salvatori, F., Romiti, M.L., Colognesi, C., Orlandi, P., Tresoldi, E., Amoroso, A., Plebani, A., Tovo, P.A., Rossi, P., Siccardi, G.A., Scarlatti, G. HIV-1 coreceptor usage and CCR5 defective allele in mother-to-child transmission. Abstracts of the 1998 Meeting of the Institute of Human Virology, Baltimore, MD, August 23-29, 1998, p 111, no 327.
109. Garred, P., Eugen Olsen, J., Iversen, A.K.N., Benfield, T.L., Svejgaard, A., Hofmann, B., Koppelhus, U., Pedersen, C., Sorensen, A.M., Katzenstein, T., Gerstoft, J., Skinhoj, P., Nielsen, J.O., Dickmeiss, E. Dual effect of CCR5 Delta 32 gene deletion in HIV-1-infected patients. Lancet 1997, 349, 1884.
110. Michael, N.L., Nelson, J.A., Kewal Ramani, V.N., Chang, G., O'Brien, S.J., Mascola, J.R., Volsky, B., Louder, M., White, G.C., Littman, D.R., Swanstrom, R.,O'Brien, T.R. Exclusive and persistent use of the entry coreceptor CXCR4 by human immunodeficiency virus type 1 from a subject homozygous for CCR5 delta32. Journal of Virology 1998, 72, 6040-6047.
111. Jekle, A., Schramm, B., Jayakumar, P., Trautner, V., Schols, D., De Clercq, E., Mills, J., Crowe, S.M., Goldsmith, M.A. Coreceptor phenotype of natural human immunodeficiency virus with nef deleted evolves in vivo, leading to increased virulence. J. Virol. 2002, 76, 6966-6973.
112. Schols, D., Claes, S., Hatse, S., Princen, K,. Vermeire, K., De Clercq, E., Skerlij, R., Bridger, G., Calandra, G.. Anti-HIV activity profile of AMD070, an orally bioavailable CXCR4 antagonist. 10th Conference on Retroviruses and Opportunistic Infections, Boston, USA, February 10-14, 2003. Abstractbook, abstract 563, p. 257.
113. Kilby, J.M., Hopkins, S., Venetta, T.M., DiMassimo, B., Cloud, G.A., Lee, J.Y., Alldredge, L., Hunter, E., Lambert, D.,
114. Lalezari, J. P., Henry, K., O'Hearn, M., Montaner, J. S., Piliero, P. J., Trottier, B., Walmsley, S., Cohen, C., Kuritzkes, D. R., Eron, J. J., Jr., Chung, J., DeMasi, R., Donatacci, L., Drobnes, C., Delehanty, J., Salgo, M. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N. Engl. J. Med. 2003, 348, 2175-2185.
115. Lazzarin, A., Clotet, B., Cooper, D., Reynes, J., Arastéh, K., Nelson, M., Katlama, C., Stellbrink, H. J., Delfraissy, J. F., Lange, J., Huson, L., DeMasi, R., Wat, C., Delehanty, J., Drobnes, C., Salgo, M. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N. Engl. J. Med. 2003, 348, 2186-2195.