title: HIV-1 RT-associated RNase H function inhibitors: Recent advances in drug development.
abstract: The HIV-1 genomic RNA reverse transcription is an essential step in the virus cycle carried out by the viral-coded reverse transcriptase (RT), which has two associated functions: the RNA- and DNA-dependent DNA polymerase (RDDP and DDDP) function and the ribonuclease H (RNase H) function. The RNase H function catalyzes the selective hydrolysis of the RNA strand of the RNA:DNA heteroduplex replication intermediate. The RT associated activities are both essential for HIV-1 replication and validated targets for drug development, but only the polymerase function has been widely investigated as drug target. In fact, either nucleoside or non-nucleoside RT inhibitors currently used in therapy act on the polymerase associated activity. In this review, we describe the compounds, reported up to today, which inhibit the HIV-1 RNase H function, their chemical structures, the structure-activity relationships and the mechanism of action.
authors.affiliation: Dept. of Applied Sciences in Biosystems, University of Cagliari, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Tramontano
authors.forename: R
authors.initials: R
authors.lastname: Di Santo
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D002626:Chemistry, Pharmaceutical / Q000639:trends*; D018360:Crystallography, X-Ray; D016503:Drug Delivery Systems; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006801:Humans; D015394:Molecular Structure; D016914:Ribonuclease H / Q000037:antagonists & inhibitors*
chemical_list: D019380:Anti-HIV Agents; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016914:Ribonuclease H