A Novel, Non-Nucleoside Inhibitor of HIV-1 Reverse Transcriptase (Review)

  • Vincent J. Merluzzi
  • Alan S. Rosenthal
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 312)


Human immunodeficiency virus type 1 (HIV-1) is the retrovirus responsible for the majority (>95%) of the acquired immunodeficiency syndrome (AIDS) cases in the world. The complicated life-cycle of this virus presents many challenging areas for intervention. Our laboratories have concentrated on prevention of the early phase in proviral synthesis, specifically interruption of the RNA > DNA metabolic process by interfering with the viral enzyme, reverse transcriptase (RT). The RT of HIV-1 is a necessary component for early proviral synthesis. This enzyme has binding sites for nucleoside triphosphates, template primer and a catalytic site for the polymerase reaction. Nucleotides are added to the polymerizing chain to create a complementary DNA molecule (for review see Gilboa et al., 1979). The most effective inhibitors of RT have been the nucleoside analogs which are converted to triphosphates by cellular enzymes and act as chain terminators of the RT reaction (Mitsuya et al., 1985). Zidovudine (3’-azido-2’-3’dideoxy-thymidine, AZT) has been shown to be of benefit in HIV-1 infected individuals (Yarchoan et al., 1986). However, there are side-effects associated with the use of AZT (Richman et al., 1987), in addition to incomplete viral inhibition (Ho et al., 1989) and viral resistance (Larder et al. 1989).


Chain Terminator Bovine Kidney Cell Fresh Peripheral Blood Mononuclear Cell Photoaffinity Probe Incomplete Viral Inhibition 
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Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Vincent J. Merluzzi
    • 1
  • Alan S. Rosenthal
    • 1
  1. 1.Boehringer Ingelheim Pharmaceuticals, Inc.RidgefieldUSA

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