title: Molecular aspects of the RT/drug interactions. Perspective of dual inhibitors.
abstract: The HIV-1 reverse transcriptase (RT) is one of the most attracting targets for the development of early phase infection inhibitors. Although many RT inhibitors have been approved for the treatment of HIV-1 infection, they all target the polymerase function of this enzyme. So far, no drugs are available for the inhibition of the RT associated ribonuclease H function (RNase H), which plays an essential role in the HIV replication cycle. Moreover it should be reported that many of the known RT inhibitors, targeting the polymerase function, enhance the RNase H activity, indicating that, although spatially distinct, a close relation occurs between the two functions. The aim of this review is to summarise the efforts in the design of new inhibitors either characterized by a novel mechanism of action or capable of blocking both RT associated functions, as well as pointing out the main binding features of the known RT inhibitors.
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Distinto
authors.forename: Elias
authors.initials: E
authors.lastname: Maccioni
authors.forename: Rita
authors.initials: R
authors.lastname: Meleddu
authors.forename: Angela
authors.initials: A
authors.lastname: Corona
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.forename: Enzo
authors.initials: E
authors.lastname: Tramontano
mesh_terms: D024882:Drug Resistance, Viral; D015497:HIV-1 / Q000187:drug effects; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D016914:Ribonuclease H / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D018894:Reverse Transcriptase Inhibitors; D016914:Ribonuclease H