title: Structure-based inhibitor design targeting HIV-1 integrase.
abstract: HIV integrase (IN) is a viral-encoded protein that catalyzes the breaking and joining reactions that mediate integration of viral DNA into the host genome. Therefore, IN offers a unique target for the development of novel anti-HIV and anti-AIDS therapeutics. To take advantage of this potential, drug discovery efforts via structure-based design approaches have been undertaken. Presented is a review of computer-aided drug design efforts targeting HIV IN. Included is an overview of the life-cycle of HIV, with emphasis on the mechanism of action of IN, biological assays for measuring IN activity and identifying IN inhibitors, and the appropriate cell-based assays required for determining the antiviral activity of IN inhibitors. This is followed by a review of the available three-dimensional structures of HIV IN. Structure-based drug design efforts are then critiqued, including both ligand-based (e.g. pharmacophore) and target-based (e.g. docking) methods. Results from recent computational chemistry studies of IN are also discussed.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20 N. Pine Street, Baltimore, MD 21201, USA. i.chen@ribotargets.com
authors.forename: I-Jen
authors.initials: IJ
authors.lastname: Chen
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
authors.forename: Alexander D
authors.initials: AD
authors.lastname: MacKerell
mesh_terms: D002384:Catalysis; D015195:Drug Design; D019427:HIV Integrase / Q000737:chemistry* / Q000187:drug effects; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*
chemical_list: D019428:HIV Integrase Inhibitors; D019427:HIV Integrase