Targeting HIV-1 protease: From peptidomimetics to non-peptide inhibitors

IDrugs

Volumn 2, Issue 4, 1999, Pages 309-320

  Gago, Federico ^a  

^a UNIVERSITY OF ALCALÁ   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

A 74704; A 77003; AMPRENAVIR; ANTIRETROVIRUS AGENT; DIDANOSINE; EFAVIRENZ; INDINAVIR; KNI 271; KYNOSTATIN 272; LAMIVUDINE; LOPINAVIR; NELFINAVIR; NEVIRAPINE; PALINAVIR; PROTEINASE; PROTEINASE INHIBITOR; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; STAVUDINE; TELINAVIR; UNCLASSIFIED DRUG; ZALCITABINE; ZIDOVUDINE;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; CONFORMATIONAL TRANSITION; DIARRHEA; DRUG APPROVAL; DRUG DESIGN; DRUG TARGETING; ENZYME STRUCTURE; FOOD AND DRUG ADMINISTRATION; HEADACHE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HYDROLYSIS; MOLECULAR MIMICRY; NAUSEA; NEPHROLITHIASIS; NONHUMAN; ORAL DRUG ADMINISTRATION; REVIEW; VIRUS GENOME; VOMITING;

EID: 0032947451     PISSN: 13697056     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (95)

1. Frankel AD, Young, JAT: HIV-1: Fifteen Proteins and an RNA. Annu Rev Biochem (1998) 67:1-25.
2. Huff JR: HIV protease: a novel chemotherapeutic target for AIDS. JMedChem (1991) 34:2305-2314.
3. Wlodawer A, Erickson JW: Structure-based inhibitors of HIV-1 protease. Annu Rev Biochem (1993) 62:543-585.
4. De Clercq E Toward improved anti-HIV chemotherapy: therapeutic strategies for intervention with HIV infections. J Med Chem (1995) 38:2491-2517.
5. West ML, Fairtie DP: Targeting HIV-1 protease: a test of drug-design methodologies. Trends Pharmacol Sei (1995) 16:67-75.
6. Sabine RE, Bender, SL: Molecular recognition of proteinligand complexes: applications to drug design. Chem Rev (1997) 97:1359-1472. Extensive review covering many design and synthetic aspects of HIV-1 protease inhibitors.
7. Kubinyi, H: Structure-based design of enzyme inhibitors and receptor ligands. Curr Op Dmg Discov Develop (1998) 1:4-15.
8. Wlodawer A, Vondrasek J: Inhibitors of HIV-1 protease: a major success of structure-assisted drug design. Annu Rev Biophys Biomol Struct (1998) 27:249-284. Updated review-covering many structural aspects of HIV-1 proteases and their complexes with inhibitors.
9. Pearl LH, Taylor WR: A structural model for the retroviral proteases Nature (1987) 329:351-354.
10. Navia MA, Fitzgerald PM, McKeever BM, et ar. Threedimensional structure of aspartyl protease from humanimmunodeficiency virus HIV-1. Nature (1989) 337:615-620.
11. Lapatto R, Blundell T, Hemmings A, Overington J, Wilderspin A, Wood S, Merson JR, Whittle PJ, Danley DE, Geoghegan KF, Hawrylik SJ, Lee SE, Scheid KG, Hobart PM: X-ray analysis of HIV-1 proteinase at 2.7 A resolution confirms structural homology among retroviral enzymes. Nature (1989)342:299-302.
12. Wagner G: The importance of being floppy. Nat Struct Biol (1995)2:255-257.
13. Vondrasek J, van Buskirk CP, Wlodawer A: Database of three-dimensional structures of HIV proteinases. Nat Struct Biol (1997) 4:8.
14. Bernstein FC, Koetzle TF, Williams GJB, Meyer E F Jr, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M: The Protein Data Bank: a computer-based archival file for macromolecular structures. J Molec Biol (1977) 112:535-542.
15. Holloway MK, Wai JM, Halgren TA, Fitzgerald PMD, Vacca JP, Dorsey BD, Levin RB, Thompson WJ, Chen U, deSoIms SJ, Gaffin N, Ghosh AK, Giuliani EA, Graham SL, Guare JP, Hungate RW, Lyle TA, Sanders WM, Tucker TJ, Wiggins M, Wiscount CM, Woltersdorf OW, Young SD, Darke PL, Zugay JA: A priori prediction of activity for HIV-1 protease inhibitors employing energy minimization in the active site. J Med Chem (1995) 38:305-317.
16. Bardi JS, Luque I, Freire E: Structure-based thermodynamic analysis of HIV-1 protease inhibitors. Biochemistry 1997, 36:6588-6596.
17. Pérez C, Ortiz AR, Pastor M, Gago F: Comparative Binding Energy analysis of HIV-1 protease inhibitors: incorporation of solvent effects and validation as a powerful tool in receptorbased drug design. J Med Chem (1998) 41:836-852.
18. Nicholson LK, Yamazaki T, Torchia DA, Grzesiek S, Bax A, Stahl SJ, Kaufman JD, Wingfield PT, Lam PY, Jadhav PK, Hodge CN, Domaille PJ, Chang C-H: Flexibility and function in HIV-1 protease. Nat Struct Bid (1995) 2:274-280.
19. Katoh I, Yasunaga T, Ikawa Y, Yoshinaka Y: Inhibition of retroviral protease activity by an aspartyl proteinase inhibitor. Nature (1987) 329:654-656.
20. Roberts NA, Martin JA, Kinchington D, Broadhurst AV, Craig JC, Duncan IB, Galpin SA, Handa BK, Kay J, Krohn A, et al: Rational design of peptide-based HIV proteinase inhibitors. Science (1990)248:358-361.
21. Krohn A, Redshaw S, Ritchie JC, Graves BJ, Hatada MH: Novel binding mode of highly potent HIV-proteinase inhibitors incorporating the (flj-hydroxyethylamine isostere. J Med Chem (1991) 34:3340-3342.
22. Vacca JP, Dorsey BD, Schleif WA, Levin RB, McDaniel SL, Darke PL, Zugay J, Quintero JC, Blahy OM, Roth E, et al: L-735,524: an orally bioavailable human immunodeficiency virus type 1 protease inhibitor. Pros NatlAcadSd USA (1994) 91:4096-4100.
23. Erickson J, Neidhart DJ, Vanbrie J, Kempf DJ, Wang XC, Norbeck DW, Plattner JJ, Rittenhouse JW, Turon M, Wideburg N, Kohlbrenner WE, Simmer R, Heifrich R, Paul DA, Knigge, M: Design, activity, and 2.8 A crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease. Sc/ence(1990) 249:527533.
24. Kempf DJ, Norbeck DW, Codacovi L, Wang XC. Kohlbrenner WE, Wideburg NE, Paul DA, Knigge MF, Vasavanonda S, CraigKennard AC, Saldivar A, Rosenbrook W Jr, Plattner JJ, Erickson J: Structure-based, C2 symmetric inhibitors of HIV protease. J Med Chem (1990) 33:2687-2689.
25. Dreyer GB, Boehm JC, Chenera B, DesJarlais RL, Hassell AM, Meek TD, Tomaszek TA Jr, Lewis M: A symmetric inhibitor binds HIV-1 protease asymmetrically. Biochemistry (1993) 32:937-947.
26. Kempf DJ, Sham HL, Marsh KC, Flentge CA, Betebenner D, Green BE, McDonald E, Vasavanonda S, Saldivar A, Wideburg NE, Kati WM, Ruiz L, Zhao C, Rno L, Patterson J, Molla A, Plattner JJ, Norbeck DW: Discovery of ritonavir, a potent inhibitor of HIV protease with high oral bioavailability and clinical efficacy. J Med Chem (1998) 41:602-617.
27. Kaldor SW, Kalish VJ, Davies JF 2nd, Shetty BV, Fritz JE, Appell K, Burgess JA, Campanale KM, Chirgadze NY, Clawson DK, Dressman BA, Hatch SD, Khalil DA, Kosa MB, Lubbehusen PP, Muesing MA, Patick AK, Reich SH, Su KS, Tatlock JH: Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. J Med Chem (1997) 40:3979-3985.
28. Kirn EE, Baker CT, Dwyer MD, Murcko MA, Rao BG, Tung RD, Navia MA: Crystal structure of HIV-1 protease in complex with VX-478, a potent and orally bioavailable inhibitor of the enzyme. JAm Chem Soc (1995) 117:1181-1182.
29. Kiso Y: Design and synthesis of substrate-based peptidomimetic human immunodeficiency virus protease inhibitors containing the hydroxymethylcarbonyl isostere. Biopcfymers (1996) 40:235-244.
30. Baldwin ET, Bhat TN, Guinik S, Uu B, Topol IA, Kiso Y, Mimoto T, Mitsuya H, Erickson JW: Structure of HIV-1 protease with KNI272, a tight-binding transition-state analog containing allophenylnorstatine. Structure (1995) 3:581-590.
31. Wang YX, Freedberg Dl, Yamazaki T, Wingfield PT. Stahl SJ, Kaufman JD, Kiso Y, Torchia DA: Solution NMR evidence that the HIV-1 protease catalytic aspartyl groups have different ionization states in the complex formed with the asymmetric drug KNI-272. Biochemistry (1996) 35:99459950.
32. Mueller BU, Anderson BD, Parley MQ, Murphy R, Zuckerman J, Jarosinski P. Godwin K, McCully CL, Mitsuya H, Pizzo PA, Balls FM: Pharmacokinetics of the protease inhibitor KNI272 in plasma and cerebrospinal fluid in nonhuman primates after intravenous dosing and in human immunodeficiency virus-infected children after intravenous and oral dosing. Antimicrob Agents Chemother (1998) 42:1815-1818.
33. Bryant M, Getman D, Smidt M. Marr J, Clare M, Dillard R, Lansky D, DeCrescenzo G, Heintz R, Houseman K, et al: SC-52151, a novel inhibitor of the human immunodeficiency virus protease. Antimicrob Agents Chemother(1995) 39:2229-2235.
34. Fischl MA, Richman DD, Flexner C, Para MF, Haubrich R, Karim A, Yeramian P, Holden-Wiltse J, Meehan PM: Phase l/ll study of the toxicity, pharmacokinetics, and activity of the HIV protease inhibitor SC-52151. J Acquir Immune Defic Syndr Hum Retrovirol (1997) 15:28-34.
35. Lamarre D, Croteau G, Wardrop E, Bourgon L, Thibeault D, Ctouette C, Vaillancourt M, Cohen E, Pargellis C, Yoakim C, Anderson PC: Antiviral properties of palinavir, a potent inhibitor of the human immunodeficiency virus type 1 protease. Ant'microb Agents Chemother (1997) 41:965-971.
36. Liard F, Jaramillo J, Paris WL, Yoakim C: Pharmacokinetic aspects of palinavir, an HIV protease inhibitor, in SpragueDawley rats. JPham So(1998) 87:782-785.
37. Thaisrivongs S, Tomich PK, Watenpaugh KD, Chong KT, Howe WJ, Yang CP, Strohbach JW, Turner SR, McGrath JP, Bohanon MJ, et al: Structure-based design of HIV protease inhibitors: 4hydroxycoumarins and 4-hydroxy-2-pyrones as non-peptidic inhibitors. J Mod Chem (1994) 37:3200-3204.
38. Bourinbaiar AS, Tan X, Nagomy R: Effect of the oral anticoagulant, warfarin, on HIV-1 replication and spread. AIDS (1993)7:129-130.
39. Turner SR, Strohbach JW, Tommasi RA, Aristoff PA, Johnson PD, Skulnick HI, Dolak LA, Seest EP, Tomich PK, Bohanon MJ. Homg MM, Lynn JC, Chong KT, Hinshaw RR, Watenpaugh KD, Janakiraman MM, Thaisrivongs S: Tipranavir (PNU-140690): a potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class. J Med Chem (1998) 41:3467-3476.
40. Poppe SM, Slade DE, Chong KT, Hinshaw RR, Pagano PJ, Markowitz M, Ho DD, Mo H, Gorman RR 3rd, Dueweke TJ, Thaisrivongs S, Tarpley WG: Antiviral activity of the dihydropyrone PNU-140690, a new nonpeptidic human immunodeficiency virus protease inhibitor. Antimicrob Agents Chemother (1997) 41:1058-1063.
41. Lunney EA, Hagen SE, Domagala JM, Humblet C, Kosinski J, Tait BD, Warmus JS, Wilson M, Ferguson D, Hupe D, et al: A novel nonpeptide HIV-1 protease inhibitor: elucidation of the binding mode and its application in the design of related analogs. J Med Chem (1994) 37:2664-2677.
42. Tait BD, Hagen S, Domagala J, Ellsworth EL, Gajda C, Hamilton HW, Prasad JV, Ferguson D, Graham N, Hupe D, Nouhan C, Tummino PJ, Humblet C, Lunney EA, Paviovsky A, Rubin J, Gracheck SJ, Baldwin ET, Bhat TN, Erickson JW, Gulnik SV, Liu B: Potent non-peptide inhibitors of HIV protease. J Med Chem (1997) 40:3781-3792.
43. Lam PY, Jadhav PK, Eyermann CJ, Hodge CN, Ru Y, Bacheler LT, Meek JL, Otto MJ, Rayner MM, Wong YN, et al: Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors. Science (1994) 263:380384.
44. Lam PY, Ru Y, Jadhav PK, Aldrich PE, DeLucca GV, Eyermann CJ, Chang CH, Emmett G, Holler ER, Daneker WF, Li L, Confalone PN, McHugh RJ, Han Q, Li R, Markwalder JA, Seitz SP, Sharpe TR, Bacheler LT, Rayner MM, Klabe RM, Shum L, Winslow DL, Komhauser DM, Jackson DA, EricksonViitanen S, Hodge CN: Cyclic HIV protease inhibitors: synthesis, conformational analysis, P2/P2' structureactivity relationship, and molecular recognition of cyclic ureas. J Med Chem (1996) 39:3514-3525.
45. Kallenbach RF III, Nugiel DA, Lam PYS, Klabe RM, Seitz SP: Stereoisomers of cyclic urea HIV-1 protease inhibitors: synthesis and binding affinities J Med Chem (1998) 41:51 ISS117.
46. Wang YX, Freedberg Dl, Grzesiek S, Torchia DA, Wingfield PT, Kaufman JD, Stahl SJ, Chang CH, Hodge CN: Mapping hydration water molecules in the HIV-1 protease/DMP323 complex in solution by NMR spectroscopy. Biochemistry (1996)35:12694-12704.
47. Hodge CN, Aldrich PE, Bacheler LT, Chang CH, Eyermann CJ, Garber S, Grubb M, Jackson DA, Jadhav PK, Korant B, Lam PY, Maurin MB, Meek JL, Otto MJ, Rayner MM, Reid C, Sharpe TR, Shum L, Winslow DL, Erickson-Viitanen S: Improved cyclic urea inhibitors of the HIV-1 protease: synthesis, potency, resistance profile, human pharmacokinetics and X-ray crystal structure of DMP 450. Chem Btol (1996) 3:301-314.
48. Jadhav PK, Ala P, Woemer FJ, Chang CH, Garber SS, Anton ED, Bacheler LT: Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV. J Med Chem (1997)40:181-191.
49. Bäckbro K, Löwgren S, Osterlund K, Atepo J, Unge T, Hülfen, BonhamNM, SchaalW, Karten A, Hallberg A: Unexpected binding mode of a cyclic sulfamide HIV-1 protease inhibitor. J Med Chem (1997) 40:898-902.
50. Kirn CD, McGee LR, Krawczyk SH, Harwood E, Harada Y, Swaminathan S, Bischofberger N, Chen MS, Cherrington JM, Xiong SF, Griffin L, Cundy KG, Lee A, Yu B, Gulnik S, Erickson JW: New series of potent, orally bioavailable, non-peptidic cyclic sulfones as HIV-1 protease inhibitors. J Med Chem (1996)39:3431-3434.
51. Jadhav PK, Woemer FJ, Lam PY, Hodge CN, Eyermann CJ, Man HW, Daneker WF, Bacheler LT, Rayner MM, Meek JL, EricksonViitanen S, Jackson DA, Calabrese JC, Schadt M, Chang CH: Nonpeptide cyclic cyanoguanidines as HIV-1 protease inhibitors: synthesis, structure-activity relationships, and Xray crystal structure studies. J Med Chem (1998) 41:1446-1455.
52. Skulnick HI, Johnson PD, Aristoff PA, Morris JK, Lovasz KD, Howe WJ, Watenpaugh KD, Janakiraman MN, Anderson DJ, Reischer RJ, Schwarte TM, Banitt LS, Tomich PK, Lynn JC, Homg MM, Chong KT, Hinshaw RR, Dolak LA, Seest EP, Schwende FJ, Rush BD, Howard GM, Toth LN, Wilkinson KR, Romines KR, et al: Structure-based design of nonpeptidic HIV protease inhibitors: the sulfonamide-substituted cyclooctylpyranones. J Med Chem (1997) 40:1149-1164.
53. Roberts NA, Craig JC, Duncan IB: HIV proteinase inhibitors. Biochem Soc Trans (1992) 20:513-516.
54. Gottesman MM, Pastan I: Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem (1993) 62:385-427.
55. Kirn RB, Fromm MF, Wandel C, Leake B, Wood AJ, Roden DM, Wilkinson GR: The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest (1998) 101:289-294.
56. Kirn AE, Dintaman JM, Waddell DS, Silverman JA: Saquinavir, an HIV protease inhibitor, is transported by Pglycoprotein. J Pharmacol Exp Ther (1998) 286:1439-1445.
57. Flexner C: HIV-protease inhibitors. N Engt J Med (1998) 338:1281-1292. Authoritative review of many clinical aspects of HIV-1 protease inhibitors containing interesting information not published in peer-reviewed journals.
58. von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW. Duan SX, Fogelman SM, Daily JP, Harmatz JS, Shader Rl: Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir. J Clin Pharmacol (1998) 38:106-111.
59. Ho DD, Toyoshima T, Mo H, Kempf DJ, Norbeck D, Chen CM, Wideburg NE, Burt SK, Erickson JW, Singh MK: Characterization, of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor. J V/ro/(1994) 68:2016-2020.
60. Tisdale M, Myers RE, Maschera B, Parry NR, Oliver NM, Blair ED: Cross-resistance analysis of human immunodeficiency virus type 1 variants individually selected for resistance to five different protease inhibitors. Antimicrob Agents Chemother (1995) 39:1704-1710.
61. Roberts JD, Bebenek K, Kunkel TA: The accuracy of reverse transcriptase from HIV-1. Science (1988) 242:1171-1173.
62. Hammond J, Larder BA, Mellors JW, Schinazi RF: The HIV Drug Resistance Database, HIV database group, Theoretical Biology and Biophysics Division, Los Alamos National Laboratory.
63. Jacobsen H, Yasargil K, Winslow DL, Craig JC, Kröhn A, Duncan IB, Mous J: Characterization of human immunodeficiency virus type 1 mutants with decreased sensitivity to proteinase inhibitor Ro 31-8959. Virology (1995)206:527-534.
64. Markowitz MM, Mo H, Kempf DJ, Norbeck DW, Bhat TN, Erickson JW, Ho DD: Selection and analysis of HIV-1 variants with increased resistance to ABT-538, a novel protease inhibitor. J V7ro/(1995) 69:701-706.
65. Pazhanisamy S, Partaledis JA, Rao BG, Livingston DJ: In vitro selection and characterization of VX-478 resistant HIV-1 variants. Adv Exp Med Biol (1998) 436:75-83.
66. Nillroth U, Vrang L, Markgren PO, Hultén J, Hallberg A, Danielson UH: Human immunodeficiency virus type 1 proteinase resistance to symmetric cyclic urea inhibitor analogs. Antimicrob Agents Chemother (1997) 41:2383-2388.
67. Smidt ML. Potts KE, Tucker SP, Blystone L, Stiebel TR Jr, Stallings WC, McDonald JJ, Pillay D, Richman DD, Bryant ML: A mutation In human immunodeficiency virus type 1 protease at position 88, located outside the active site, confers resistance to the hydroxyethylurea inhibitor SC55389A. Antimicrob Agents Chemother (1997) 41:515-522.
68. Gong Y-L, Robinson BS, Rose R, Riccardi K, Deminie C, et al: Anti-viral activity and resistance profile of an HIV-1 protease inhibitor BMS-232632. The 38th Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 98), San Diego, CA (1998).
69. Klabe RM, Bacheler LT, Ala PJ, Erickson-Viitanen S, Meek JL: Resistance to HIV protease inhibitors: a comparison of enzyme inhibition and antiviral potency. Biochemistry (1998)37:8735-8742.
70. Carrillo A, Stewart KD, Sham HL, Norbeck DW, Kohlbrenner WE, Leonard JM, Kempf DJ, Molla A: In vitro selection and characterization of human immunodeficiency virus type 1 variants with increased resistance to ABT-378, a novel protease inhibitor. J V7ro/(1998) 72:7532-7541.
71. Schinazi RF, Larder BA, Mellors JW: Mutations in retroviral genes associated with drug resistance. Int Antiviral News (1996), 4:95-107.
72. Ala PJ, Huston EE, Klabe RM, McCabe DD, Duke JL, Rizzo CJ, Korant BD, DeLoskey RJ, Lam PY, Hodge CN, Chang CH: Molecular basis of HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with cyclic urea inhibitors. Biochemistry (\997) 36:1573-1580.
73. tuque I, Todd MJ, Gömez J, Semo N, Freire E: Molecular basis of resistance to HIV-1 protease inhibition: a plausible hypothesis. Biochemistry (1998) 37:5791-5797.
74. Rose RB, Craik CS, Stroud RM Domain flexibility in retroviral proteases: structural implications for drug resistant mutations. öchem/suy(1998) 37:2607-2621.
75. Lech WJ, Wang G, Yang YL, Chee Y, Dorman K, McCrae D, Lazzeroni LC, Erickson JW, Sinsheimer JS, Kaplan AH: In vivo sequence diversity of the protease of human immunodeficiency virus type 1: presence of protease inhibitor-resistant variants in untreated subjects. J W/o/(1996) 70:2038-2043.
76. Boucher C: Rational approaches to resistance: using saquinavir. AIDS (1996) Suppl 1 :S15-S19.
77. Condra JH, Schleif WA, Blahy OM, Gabryelski U, Graham DJ, Quintero JC.'Rhodes A, Robbins HL, Roth E, Shivaprakash M, et al: In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature (1995) 374:569-571.
78. Schmit JC, Ruiz L, Clotet B, Raventos A, Tor J, Leonard J, Desmyter J, De Clercq E, Vandamme AM: Resistance-related mutations in the HIV-1 protease gene of patients treated for 1 year with the protease inhibitor ritonavir (ABT-538). AIDS (1996)10:995-999.
79. Media A, Komeyeva M, Gao Q, Vasavanonda S, Schipper PJ, Mo HM, Markowitz M, Chemyavskiy T, Niu P, Lyons N, Hsu A, Granneman GR, Ho DD, Boucher CA, Leonard JM, Norbeck DW, Kempf DJ: Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nat Med (1996) 2:760-766.
80. Pafck AK, Boritzki TJ, Bloom LA: Activities of the human immunodeficiency virus type 1 (HIV-1) protease inhibitor nelfinavir mesylate in combination with reverse transcriptase and protease inhibitors against acute HIV-1 infection in vitro. Antimicrob Agents Chemother (1997) 41:2159-2164.
81. Carpenter CC, Fischl MA, Hammer SM, Hirsch MS, Jacobsen DM, Katzenstein DA, Montaner JS, Ftichman DD, Saag MS, Schooley RT, Thompson MA, Velia S, Yeni PG, Volberding PA: Antiretroviral therapy for HIV infection in 1998: updated recommendations of the International AIDS Society-USA Panel. JAMA (1998) 280:78-86.
82. Moyle GJ, Gazzard BG, Cooper DA, Gatell J: Antiretroviral therapy for HIV infection. A knowledge-based approach to drug selection and use. Drugs (1998) 55:383-404.
83. Chong KT, Pagano PJ: In vitro combination of PNU-140690, a human immunodeficiency virus type 1 protease inhibitor, with ritonavir against ritonavir-sensitive and -resistant clinical isolates. Antimicrob Agents Chemother (1997) 41:2367-2373.
84. St Clair MH, Millard J, Rooney J, Tisdal M, Parry N, Sadler BM, Blum MR, Painter G: In vitro antiviral activity of 141W94 (VX-478) in combination with other antiretroviral agents. Antiviral Res (1996) 29:53-56.
85. Molla A, Kohlbrenner WE: Resistance to antiretroviral drug therapy. Ann Rep Med Chem (1997) 32:131-140.
86. Havlir DV, Lange JM: New antiretrovirals and new combinations. AIDS (1998) 12 (Suppl A):S165-74.
87. Panel on Clinical Practices for Treatment of HIV Infection: Guidelines for the Use of Antiretroviral Agents in HIVInfected Adults and Adolescents. HIV/AIDS Treatment Information Service (1999).
88. Deeks SG, Smith M, Holodniy M, Kahn JO: HIV-1 protease inhibitors. A review for clinicians. JAMA (1997) 277:145153.
89. Mann JM, Tarantola DJ: HIV 1998: the global picture. Sei Am (1998)279:82-83.
90. Hirsch MS, Conway B, D'Aquila RT, Johnson VA, Brun-Vézinet F, Clotet B, Demeter LM, Hammer SM, Jacobsen DM, Kuritzkes DR, Loveday C, Mellors JW, Vella S, Richman DD: Antiretroviral drug resistance testing in adults with HIV infection: implications for clinical management. International AIDS Society-USA Panel JAMA (1998) 279:1984-1991.
91. Mellors JW: Viral load tests provide valuable answers. Sei Am (1998) 279:70.
92. Schräger LK, D'Souza MP: Cellular and anatomical reservoirs of HIV-1 in patients receiving potent antiretroviral combination therapy. JAMA (1998) 280:67-71.
93. Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H, Hermankova M, Chadwick K, Margolick J, Quinn TC, Kuo YH, Brookmeyer R, Zeiger MA, Barditch-Crovo P, Siliciano RF: Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature (1997) 387:183-188.
94. Bold G, Fässler A, Capraro HG, Cozens R, Klimkait T, Lazdins J, Mestan J, Poncioni B, Rösel J, Stover D, Tinteinot-Blomley M, Acemoglu F, Beck W, Boss E, Eschbach M, Hürtimann T, Masso E, Roussel S, Ucci-Stoll K, Wyss D, Lang M: New azadipeptide analogues as potent and orally absorbed HIV-1 protease inhibitors: candidates for clinical development. J Med Chem (1998) 41:3387-3401.
95. Kraulis PJ: Molscript: a program to produce both detailed and schematic plots of protein structures. J Appl Crystall (1991)24:946-950.