Nonnucleoside Inhibitors of HIV-1 Reverse Transcriptase: Nevirapine as a Prototype Drug

AIDS Research and Human Retroviruses

Volumn 8, Issue 2, 1992, Pages 145-152

  Grob, Peter M ^a   wu, Joe C ^a   Cohen, Kenneth A ^a   Ingraham, Richard H ^a   Shih, Cheng Kon ^a   Hargrave, Karl D ^a   Mctague, Tari L ^a   Merluzzi, Vincent J ^a  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; L 693593; NEVIRAPINE; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

DRUG RESISTANCE; ENZYME INHIBITION; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; NONHUMAN; REVIEW;

AMINO ACID SEQUENCE; ANIMAL; AZEPINES; BINDING SITES; DRUG RESISTANCE, MICROBIAL; HIV-1; HUMAN; MOLECULAR SEQUENCE DATA; MUTAGENESIS, SITE-DIRECTED; NEVIRAPINE; PYRIDINES; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 0026607918     PISSN: 08892229     EISSN: 19318405     Source Type: Journal    
DOI: 10.1089/aid.1992.8.145     Document Type: Article

References (35)

1. Gilboa E, Mitra SW, Goff S, and Baltimore D: A detailed model of reverse transcriptase and tests of crucial aspects. Cell 1989; 18:93–100.
2. Yarchoan R, Klecker RW, Weinhold KJ, Markham PD, Lyerly HK, Durack DT, Gelman E, Lehrman SN, Blum RM, Barry DW, Shearer GM, Fischl M, Mitsuya H, Gallo RC, Collins J, Bolognesi D, Myers C, and Broder S: Administration of 3′-azido-3′-deoxythymidine, an inhibitor of HTLVIII/LAV replication, to patients with AIDS or AIDS-related complex. Lancet 1986;1:575–580.
3. Kedar PS, Abbots J, Kovacs T, Lesiak K, Torrence P, and Wilson SH: Mechanism of HIV reverse transcriptase: enzyme-primer interaction as revealed through studies of a dNTP analog, 3′-azido-dTTP. Biochemistry 1990;29:3603–3611.
4. Huang P, Farquhar D, and Plunkett W: Selective action of 3′-azido-3′-deoxythymidine 5′-triphosphate on viral reverse transcriptases and human DNA polymerases. J Biol Chem 1990;265:11914–11918.
5. Richman DD, Fischl MA, Grieco MH, Gottlieb MS, Volberding PA, Laskin OL, Leedom JM, Groopman JE, Mildvan D, Hirsch M, Jackson GG, Durack DT, and Nusinoff-Lehrman SN: The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med 1987:317:192–197.
6. Dalakas MC, Illa I, Pezeshkpour GH, Laukaitis JP, Cohen B, and Griffin JL: Mitochondrial myopathy caused by long-term zidovudine therapy. N Engl J Med 1990;322:1098–1105.
7. Lambert JS, Seidlin M, Reichman RC, Plank CS, Laverty M, Morse GD, Knupp C, McLaren C, Pettinelli C, Valentine FT, and Dolin R: 2′,3′-dideoxyinosine (ddI) in patients with acquired immunodeficiency syndrome or AIDS-related complex. A phase I trial. N Engl J Med 1990;322:1333–1340.
8. Carmine AA and Brogden RN: Pirenzepine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in peptic ulcer disease and other allied diseases. Drugs 1985;30:85–126.
9. Merluzzi VJ, Hargrave KD, Labadia M, Grozinger K, Skoog M, Wu JC, Shih C-K, Eckner K, Hattox S, Adams J, Rosenthal AS, Faanes R, Eckner RJ, Koup RA, and Sullivan JL: Inhibition of HIV-1 replication by a non-nucleoside reverse transcriptase inhibitor. Science 1990;250:1411–1413.
10. Skoog MT, Hargrave KD, Miglietta JJ, Kopp EB, and Merluzzi VJ: Inhibition of HIV-1 reverse transcriptase and virus replication by a non-nucleoside dipyridodiazepinone BI-RG-587. Med Res Rev. In Press.
11. Koup RA, Merluzzi VJ, Hargrave KD, Adams J, Grozinger K, Eckner RJ, and Sullivan JL: Inhibition of human immunodeficiency virus Type 1 (HIV-1) replication by the dipyridodiazepinone BI-RG-587. J Infect Dis 1991;163:966–970.
12. Richman D, Rosenthal AS, Skoog M, Eckner RJ, Chou T-C, Sabo, JP, and Merluzzi VJ: BI-RG-587 is active against zidovudine-resistant human immunodeficiency virus type 1 and synergistic with zidovudine. Antimicrob Agents and Chemother 1991:35:305–308.
13. Moore MAS and Merluzzi VJ: Comparison of a non-nucleoside HIV-1 reverse transcriptase inhibitor and zidovudine on human bone marrow progenitors. Blood (Submitted).
14. Hargrave KD, Proudfoot JR, Grozinger KG, Cullen E, Kapadia SR, Patel UR, Fuchs VU, Mauldin SC, Vitous J, Behnke ML, Klunder JM, Pal K, Skiles JW, McNeil DW, Rose JM, Chow GC, Skoog MT, Wu JC, Schmidt G, Engel WW, Eberlein WG, Saboe TD, Campbell SJ, Rosenthal AS, and Adams J: Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 1. Tricyclic pyridobenzo- and dipyridodiazepinones. J Med Chem 1991;34: 2231–2241.
15. Wu JC, Warren TC, Adams J, Proudfoot J, Skiles J, Raghavan P, Perry C, Potocki I, Farina FR, and Grob PM: A Novel Dipyridodiazepinone inhibitor of HIV-1 reverse transcriptase acts through a nonsubstrate site. Biochemistry 1991;30:2022–2026.
16. Cheng N, Painter GR, and Fruman PA: Crosslinking of Substrates occurs exclusively to the p66 subunit of heterodimeric HIV-1 reverse transcriptase. Biochem Biophys Res Comm 1991; 174:785–789.
17. Furfine ES and Reardon JE: Human immunodeficiency virus reverse transcriptase ribonuclease H: Specificity of tRNALys3-primer excision. Biochemistry 1991;30:7041–7046.
18. Jacobo-Molina A and Arnold E: HIV reverse transcriptase structure-function relationships. Biochemistry 1991;30:6352–6361.
19. Furfine ES and Reardon JE: Reverse transcriptase-RNase H from the human immunodeficiency virus: Relationship of the DNA polymerase and RNA hydrolysis activity. J Biol Chem 1991;266:406–412.
20. Wohrl BM and Moelling K: Interaction of HIV-1 ribonuclease H with polypurine tract containing RNA-DNA hybrids. Biochemistry 1990;29:10141–10147.
21. Pauwels R, Andries K, Desmyter J, Schols D, Kukla MJ, Breslin HJ, Raeymaeckers A, VanGelder J, Woesteinborghs R, Heykants J, Schellekens K, Janssen MA, DeClercq E, and Janssen PA: Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives. Nature 1990;343:470–474.
22. Baba M, DeClercq E, Tanaka H, Ubasawa M, Takashima H, Sekiya K, Nitta I, Umezu K, Nakashima H, Mori S, Shigeta S, Walder RT, and Miyasaka T: Potent and selective inhibition of human immunodeficiency virus type 1 (HIV-1) by 5-ethyl-6-phenylthiouracil derivatives through their interaction with the HIV-1 reverse transcriptase. Proc Natl Acad Sci (USA) 1991;88:2356–2360.
23. Goldman ME, Nunberg JH, O'Brien JA, Quintero JC, Schleif WA, Freund KF, Gaul SI, Saari WS, Wai JS, Hoffman JM, Anderson PS, Hupe DJ, Emini EA, and Stern AM: Pyridinone derivatives: Specific human immunodeficiency virus type 1 reverse transcriptase inhibitors with antiviral activity. Proc Natl Acad Sci (USA) 1991;88;6863–6867.
24. Cohen KA, Hopkins J, Ingraham RH, Pargellis C, Wu JC, Palladino DEH, Kinkade P, Warren TC, Rogers S, Adams J, Farina PR, and Grob PM: Characterization of the binding site for nevirapine (BI-RG-587), a non-nucleoside inhibitor of human immunodeficiency virus type-1 reverse transcriptase. J Biol Chem 1991;266:14670–14674.
25. Argos P: A sequence motif in many polymerases. Nucl Acids Res 1988;16:9909–9916.
26. Delarue M, Poch O, Tordo N, Moras D, and Argos P: An attempt to unify the structure of polymerases. Protein Eng 1990;3:461–467.
27. Webster TA, Patarca R, Lathrop RH, and Smith TF: Potential structural motifs for reverse transcriptases. Mol Biol Evol 1989;6:317–320.
28. Lowe DM, Parmar V, Kemp SD, and Larder BA: Mutational analysis of two conserved sequence motifs in HIV-1 reverse transcriptase. FEBS 1991;282:231–234.
29. DeVico AL, Copeland TD, DiMarzo Veronese F, Oroszlan S, Gallo RC, and Sarngadharan MG: Purification and partial characterization of human immunodeficiency virus type 2 reverse transcriptase. AIDS Res Human Retroviruses 1989;5:51–60.
30. LeGrice SF, Zehnle R, and Mous J: A single 66-kilodalton polypeptide processed from the human immunodeficiency virus type 2 pol polyprotein in Escherichia coli displays reverse transcriptase activity. J Virol 1988;62:2525–2529.
31. Hizi A, Tal R, and Hughes SH: Mutational analysis of the DNA polymerase and ribonuclease H activities of human immunodeficiency virus type 2 reverse transcriptase expressed in Escherichia coli. Virology 1991;180:339–346.
32. Meyers G, Rabson AB, Berzofsky JA, Smith TF, and Wong-Staal F (Eds.): Human Retroviruses and AIDS, A Compilation and Analysis of Nucleic Acid and Amino Acid Sequences. Theoretical Biology and Biophysics, Los Alamos, NM, 1990.
33. Shih C-K, Rose JM, Hansen GL, Wu JC, Bacolla A, and Griffin JA: Chimeric substitutions in HIV-1/HIV-2 reverse transcriptase alters sensitivity to nevirapine. Proc Natl Acad Sci 1991;88:9878–9882.
34. Nunberg JH, Schleif WA, Boots EJ, O'Brien JA, Quintero JC, Hoffman JM, Emini EA, and Goldman ME: Viral resistance to human immunodeficiency virus type 1-specific pyridinone reverse transcriptase inhibitors. J Virol 1991;65:4887–4892.
35. Richman D, Shih C-K, Lowy I, Rose J, Prodanovich P, Goff S, and Griffin J: HIV-1 mutants resistant to non-nucleoside inhibitors of reverse transcriptase arise in tissue culture. Proc Natl Acad Sci 1991;88:11241–11245.