Sensitivity and resistance to (+)-calanolide A of wild-type and mutated forms of HIV-1 reverse transcriptase

Antivir Ther. 1999;4(4):203-9.


We have tested both wild-type and drug-resistant mutated, recombinant human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) molecules for sensitivity to each of two non-nucleoside RT inhibitors (NNRTI), (+)-calanolide A and nevirapine, in primer extension assays. We found that RT containing either the V106A or Y181C substitutions, associated with NNRTI resistance, displayed approximately 90-fold resistance to nevirapine but remained fully sensitive to (+)-calanolide A and that the Y181C mutation marginally enhanced susceptibility to the latter drug. In contrast, the Y188H substitution in RT resulted in about 30-fold resistance to (+)-calanolide A in these assays but did not result in diminished sensitivity to nevirapine. Tissue culture results indicated that the combination of (+)-calanolide A and nevirapine possessed an additive to weakly synergistic effect in blocking replication of HIV-1 in tissue culture. These results suggest that (+)-calanolide A and nevirapine might have rationale as a combination therapy for HIV disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coumarins / pharmacology*
  • Drug Resistance
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / genetics*
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • Mutation
  • Nevirapine / pharmacology
  • Pyranocoumarins
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Virus Replication / drug effects


  • Coumarins
  • Pyranocoumarins
  • Reverse Transcriptase Inhibitors
  • Nevirapine
  • HIV Reverse Transcriptase
  • calanolide A