Inhibition of human immunodeficiency virus type 1 wild-type and mutant reverse transcriptases by the phenyl ethyl thiazolyl thiourea derivatives trovirdine and MSC-127

Antiviral Res. 1995 Dec;28(4):331-42. doi: 10.1016/0166-3542(95)00056-9.


A new class of very potent and selective non-nucleoside inhibitors of HIV reverse transcriptase (RT) has recently been identified. The prototype compound trovirdine (LY 300046 HCl) and one analogue, MSC-127, have been studied with respect to inhibition of wild-type HIV-1 RT and RT with various mutations known to give rise to resistance to other non-nucleoside RT inhibitors, namely Leu100-->Ile (Ile100), Glu138-->Arg (Arg138), Tyr181-->Cys (Cys181) and Tyr188-->His (His188). The inhibition of HIV-1 RT by trovirdine and MSC-127 was reversible and template dependent. Trovirdine inhibited HIV-1 RT with an IC50 of 0.007 microM when employing heteropolymeric primer/template (oligo-DNA/ribosomal RNA) and dGTP as substrate. Enzyme kinetic studies showed that inhibition of RT by trovirdine was non-competitive with regard to deoxynucleoside triphosphates and uncompetitive with respect to varied primer/template under steady-state conditions. The amino acid changes Leu100, Tyr181 and Tyr188 gave rise to 25-, 147- and 12-fold decrease in inhibition by trovirdine. Enzyme-kinetic studies on trovirdine have been carried out using various RT mutants and compared to the properties of the earlier reported non-nucleoside RT inhibitors 9-Cl-TIBO, nevirapine and L-697,661.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Base Sequence
  • Enzyme Activation
  • HIV Reverse Transcriptase
  • HIV-1 / enzymology*
  • Kinetics
  • Molecular Sequence Data
  • Mutation
  • Pyridines / pharmacology*
  • RNA-Directed DNA Polymerase / drug effects*
  • RNA-Directed DNA Polymerase / genetics
  • RNA-Directed DNA Polymerase / metabolism
  • Reverse Transcriptase Inhibitors / pharmacology
  • Thiourea / analogs & derivatives*
  • Thiourea / pharmacology


  • Antiviral Agents
  • MSC 127
  • Pyridines
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase
  • Thiourea
  • trovirdine