Human immunodeficiency virus inhibitor

DRUGS ACTIVE AGAINST HUMAN IMMUNODEFICIENCY VIRUS INHIBITORS OF HIV FUSION [SEDA-28, 337 SEDA-29, 310]... 

CarriUo A, Stewart KD, Sham HL, Norbeck DW, Kohlbrenner WE, Leonard JM, Kempf DJ, Molla A (1998) In vitro selection and characterization of human immunodeficiency virus type 1 variants with increased resistance to ABT-378, a novel protease inhibitor. J Virol 72 7532-7541 Chambers TJ, Nestorowicz A, Amberg SM, Rice CM (1993) Mutagenesis of the yellow fever virus NS2B protein effects on proteolytic processing, NS2B-NS3 complex formation, and viral replication. J Virol 67 6797-6807... 

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Johnston E, Winters MA, Rhee SY, Merigan TC, Schiffer CA, Shafer RW (2004) Association of a novel human immunodeficiency virus type 1 protease substrate cleft mutation, L23I, with protease inhibitor therapy and in vitro drug resistance. Antimicrob Agents Chemother 48 4864 868... 

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The first lead compounds for non-nucleoside reverse transcriptase (RT) inhibitors (NNRTl) were discovered about 15 years ago (Pauwels et al. 1990 Merluzzi et al. 1990 Goldman et al. 1991 De Clercq 1993 Riibsamen-Waigmann et al. 1997). Since then they have become an important ingredient of the dmg combination schemes that are currently used in the treatment of human immunodeficiency virus type 1 (HlV-1) infections. Starting from the HEPT and TIBO derivatives, numerous classes of compounds have been described as NNRTIs. Four compounds (nevirapine, delavirdine, efavirenz and etravirine) have so far been approved for clinical use and several others are the subject of clinical trials (Balzarini 2004 Stellbrink 2007). 

In this chapter, we have described the spectrum of antiviral activities that have been discovered beyond the world of nucleoside analogues, protease and fusion inhibitors. The compounds and mechanisms described here may one day add significantly to the armamentarium of antiviral agents, not only against Herpes Simplex, Hepatitis B and Human Immunodeficiency Virus, but also against Hepatitis C and Human Cytomegalovirus. 

De Clercq E (1993) HlV-l-spedfic RT inhibitors highly selective inhibitors of human immunodeficiency virus type 1 that are specifically targeted at the viral reverse transcriptase. Med Res Rev 13 229-258... 

Gibson W (1996) Structure and assembly of the virion. Intervirology 39 389 00 Goldman ME, Nunberg JH, O Brien JA, Quintero JC, Schleif WA, Freund KF, Gaul SL, Saari WS, Wai IS, Hoffman JM et al. (1991) Pyridinone derivatives specific human immunodeficiency virus type 1 reverse transcriptase inhibitors with antiviral activity. Proc Natl Acad Sci USA... 

Kehlenbeck S, Betz U, Birkmann A, Fast B, Goller AH, Henninger K, Lowinger T, Marrero D, Paessens A, Paulsen D, Pevzner V, Schohe-Loop R, Tsujishita H, Welker R, Kreuter J, Riibsamen-Waigmann H, Dittmer F (2006) Dihydroxythiophenes are novel potent inhibitors of human immunodeficiency virus integrase with a diketo acid-like pharmacophore. J Virol... 

Shimura K, Kodama E, Sakagami Y, Matsuzaki Y, Watanabe W, Yamataka K, Watanabe Y, Ohata Y, Doi S, Sato M, Kano M, Ikeda S, Matsuoka M (2008) Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). J Virol 82 764-774... 

Many enveloped viruses share a common mechanism of fusion, mediated by a virus-encoded glycoprotein that contains heptad repeats in its extraceUnlar domain. Dnring the fnsion process, these domains rearrange to form highly structured and thermodynamically stable coiled-coils. Viruses encoding fusion proteins that have these domains inclnde members of the paramyxovirus family (e.g., respiratory syncytial virus, metapneumovirus, and measles virus), ebola virus, influenza, and members of the retroviridae (e.g., human T cell lenkemia virus type-1 and human immunodeficiency virus type-1, HlV-1). Peptide inhibitors of fusion that disrupt the... 

Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR (1996) Identification of a major co-receptor for primary isolates of HIV-1. Nature 381 661-666 Derdeyn CA, Decker JM, Sfakianos JN, Wu X, O Brien WA, Ratner L, Kappes JC, Shaw GM, Hunter E (2000) Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gpl20. J Virol 74 8358-8367... 

Ho HT, Fan L, Nowicka-Sans B, McAuhffe B, li CB, Yamanaka G, Zhou N, Fang H, Dicker 1, Dalterio R, Gong YF, Wang T, Yin Z, Ueda Y, MatiskeUa J, Kadow J, Qapham P, Robinson J, Colonno R, Lin PF (2006) Envelope conformational changes induced by human immunodeficiency virus type 1 attachment inhibitors prevent CD4 binding and downstream entry events. 

Jacobson JM, Lowy 1, Fletcher CV, O NeUl TJ, Tran DN, Ketas TJ, Trkola A, Klotman ME, Maddon PJ, Olson WC, Israel RJ (2000) Single-dose safety, pharmacology, and antiviral activity of the human immunodeficiency virus (HIV) type 1 entry inhibitor PRO 542 in HIV-infected adults. J Infect Dis 182 326-329... 

Platt EJ, Dumin IP, Rabat D (2005) Kinetic factors control efficiencies of cell entry, efficacies of entry inhibitors, and mechanisms of adaptation of human immunodeficiency virus, J Virol 79 4347 356... 

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