Publication | Closed Access
Crystal Structures of HIV-1 Reverse Transcriptase with Etravirine (TMC125) and Rilpivirine (TMC278): Implications for Drug Design
224
Citations
0
References
2010
Year
Biomolecular Structure PredictionMolecular BiologyAntiviral DrugResistance MutationsDrug ResistanceDrug DesignHuman RetrovirusInherent FlexibilityAntiviral Drug DevelopmentResistance Mutation (Virology)Hiv-1 Reverse TranscriptaseHivStructural BiologyBiomolecular EngineeringMolecular DockingNatural SciencesCrystal StructuresMedicineDrug Discovery
Diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitors (NNRTIs) have inherent flexibility, helping to maintain activity against a wide range of resistance mutations. Crystal structures were determined with wild-type and K103N HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278). These structures reveal a similar binding mode for TMC125 and TMC278, whether bound to wild-type or K103N RT. Comparison to previously published structures reveals differences in binding modes for TMC125 and differences in protein conformation for TMC278.