title: Structure-enhanced methods in the development of non-nucleoside inhibitors targeting HIV reverse transcriptase variants.
abstract: Resistance continues to emerge as a leading cause for antiretroviral treatment failure. Several mutations in HIV reverse transcriptase (RT) confer resistance to non-nucleoside inhibitors (NNRTIs), vital components of antiretroviral combination therapies. Since the majority of mutations are located in the NNRTI binding pocket, crystal structures of RT variants in complex with NNRTIs have provided ideas for new drug design strategies. This article reviews the impact of RT crystal structures on the multidisciplinary design and development of new inhibitors with improved resistance profiles.
authors.affiliation: Division of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy & Health Sciences, Long Island University, 75 Dekalb Avenue, Brooklyn, NY 11201, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Frey
mesh_terms: D019380:Anti-HIV Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D024882:Drug Resistance, Viral; D006678:HIV / Q000187:drug effects* / Q000201:enzymology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D062105:Molecular Docking Simulation; D009154:Mutation; D011487:Protein Conformation; D018894:Reverse Transcriptase Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology*; D012641:Selection, Genetic
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase
keywords: conserved residues; main chain interactions; resistance variants