title: Targeting HIV-1 integrase with strand transfer inhibitors.
abstract: HIV-1 integrase (IN) is a retroviral enzyme essential for integration of genetic material into the DNA of the host cell and hence for viral replication. The absence of an equivalent enzyme in humans makes IN an interesting target for anti-HIV drug design. This review briefly overviews the structural and functional properties of HIV-1 IN. We analyze the binding modes of the established drugs, clinical candidates and a comprehensive library of leads based on innovative chemical scaffolds of HIV-1 IN strand transfer inhibitors (INSTIs). Computational clustering techniques are applied for identifying structural features relating to bioactivity. From bio- and chemo-informatics analyses, we provide novel insights into structure-activity relationships of INSTIs and elaborate new strategies for design of innovative inhibitors.
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, 15 BeiSanHuan East Road, P.O. Box 53, Beijing 100029, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, 15 BeiSanHuan East Road, P.O. Box 53, Beijing 100029, PR China.
authors.forename: Shouyi
authors.initials: S
authors.lastname: Xuan
authors.affiliation: Beijing Key Lab of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, 15 BeiSanHuan East Road, P.O. Box 53, Beijing 100029, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, 15 BeiSanHuan East Road, P.O. Box 53, Beijing 100029, PR China. Electronic address: yanax@mail.buct.edu.cn.
authors.forename: Aixia
authors.initials: A
authors.lastname: Yan
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D020134:Catalytic Domain; D016000:Cluster Analysis; D019295:Computational Biology; D017076:Computer-Aided Design; D015195:Drug Design; D019427:HIV Integrase / Q000737:chemistry / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D008024:Ligands; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1