title: HIV-1 integrase and RNase H activities as therapeutic targets.
abstract: The retroviruses are a large, diverse family of enveloped RNA viruses defined by their structure, composition and replicative properties. The hallmark of the family is its replicative strategy, essential steps of which include reverse transcription of the viral RNA and the subsequent integration of this DNA into the genome of the cell. These steps are performed by two viral-encoded enzymes, reverse transcriptase (RT), which possesses DNA polymerase and ribonuclease H (RNase H) activities, and integrase (IN). These enzymes are excellent targets for retroviral therapy since they are essential for viral replication. Numerous substances capable of inhibiting the DNA polymerase activity of HIV-1 RT are available, while few specific inhibitors of RNase H activity have been described. IN is absolutely necessary for stable and productive infection of cells. Some IN inhibitors have been recently reported and are available demonstrating the potential of IN as an antiviral target. This paper is an overview of the inhibitors of RNase H and IN and describes the most promising inhibitors.
authors.affiliation: Laboratory of Replication and Expression of Eukaryotic and Retroviral Genomes, UMR 5097, CNRS-Université Victor Segalen Bordeaux 2, France. marie-line.andreola@reger.u-bordeaux2.fr
authors.forename: M L
authors.initials: ML
authors.lastname: Andréola
authors.forename: V Richard
authors.initials: VR
authors.lastname: De Soultrait
authors.forename: M
authors.initials: M
authors.lastname: Fournier
authors.forename: V
authors.initials: V
authors.lastname: Parissi
authors.forename: C
authors.initials: C
authors.lastname: Desjobert
authors.forename: S
authors.initials: S
authors.lastname: Litvak
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015658:HIV Infections / Q000188:drug therapy*; D019427:HIV Integrase / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016914:Ribonuclease H / Q000037:antagonists & inhibitors* / Q000737:chemistry; D052156:SELEX Aptamer Technique; D012441:Saccharomyces cerevisiae; D016662:Virus Integration / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D011993:Recombinant Fusion Proteins; D018894:Reverse Transcriptase Inhibitors; D019427:HIV Integrase; D054303:HIV Reverse Transcriptase; D016914:Ribonuclease H