Specific inhibition of the reverse transcriptase of human immunodeficiency virus type 1 and the chimeric enzymes of human immunodeficiency virus type 1 and type 2 by nonnucleoside inhibitors

Antimicrob Agents Chemother. 1993 May;37(5):1037-42. doi: 10.1128/aac.37.5.1037.

Abstract

We have studied the effects of four nonnucleoside inhibitors, including the novel natural product inhibitor calanolide A, on molecular chimeras containing complementary segments of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) reverse transcriptases (RTs). All four compounds specifically inhibited the DNA polymerase activity of HIV-1 RT but had no apparent effect on the RNase H activity of this enzyme or on the DNA polymerase or RNase H activity of HIV-2 RT. Three of these compounds showed the generally expected patterns of resistance and susceptibility with the various chimeric RTs. However, the inhibition patterns of the chimeric RTs by calanolide A provided evidence that there is a segment between residues 94 and 157 in HIV-1 RT that is critical for inhibition. However, the data also suggest that there may be a second segment located between amino acids 225 and 427 in HIV-1 RT that is also important for specifying susceptibility to the drug.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Coumarins / pharmacology*
  • HIV Reverse Transcriptase
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • HIV-2 / drug effects
  • HIV-2 / enzymology*
  • Mutagenesis, Insertional
  • Pyranocoumarins
  • RNA-Directed DNA Polymerase / genetics
  • Recombinant Fusion Proteins / antagonists & inhibitors*
  • Recombinant Fusion Proteins / genetics
  • Reverse Transcriptase Inhibitors*

Substances

  • Antiviral Agents
  • Coumarins
  • Pyranocoumarins
  • Recombinant Fusion Proteins
  • Reverse Transcriptase Inhibitors
  • reverse transcriptase, Human immunodeficiency virus 2
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase
  • calanolide A