title: Past and future. Current drugs targeting HIV-1 integrase and reverse transcriptase-associated ribonuclease H activity: single and dual active site inhibitors.
abstract: Catalytic HIV type-1 (HIV-1) integrase (IN) and ribonuclease H (RNase H) domains belong to the polynucleotidyl transferase superfamily and are characterized by highly conserved motifs that coordinate two divalent Mg(2+) cations and are attractive targets for new antiviral agents. Several structural features of both domains are now available. Drugs targeting the HIV-1 IN are currently approved for anti-HIV therapy, while no drug targeting the HIV-1 RNase H function is yet available. This review describes HIV-1 IN and the RNase H function and structures, compounds targeting their active sites and dual inhibition as a new approach for drug development.
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Esposito
authors.forename: Enzo
authors.initials: E
authors.lastname: Tramontano
mesh_terms: D020134:Catalytic Domain / Q000187:drug effects; D055808:Drug Discovery; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D019427:HIV Integrase / Q000737:chemistry / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D016914:Ribonuclease H / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D019428:HIV Integrase Inhibitors; D019427:HIV Integrase; D054303:HIV Reverse Transcriptase; D016914:Ribonuclease H; C514801:p31 integrase protein, Human immunodeficiency virus 1