title: Blocking nuclear import of pre-integration complex: an emerging anti-HIV-1 drug discovery paradigm.
abstract: Although recent progress in highly active antiretroviral therapy (HAART) has provided an effective way to treat AIDS patients, the emergence of drug-resistant HIV-1 strains and drug toxicity during long-term treatment of HIV-infected patients necessitate the search for new targets that can be used to develop novel antiviral agents. One such target is the nuclear import process of the HIV pre-integration complex (PIC). The ability of HIV-1 using host cell nuclear import machinery to translocate the viral PIC into the cell nucleus is the critical determinant in the replication of the virus in non-dividing cells, such as macrophages. Compounds inhibiting HIV-1 nuclear import may be attractive candidates for novel anti-HIV development. In this review, we will describe the mechanisms of HIV-1 PIC translocation into the nucleus and the structure-function of the viral and cellular factors involved in this process, as well as several classes of novel anti-HIV compounds which target the nuclear import of HIV-1 PIC and effectively block viral replication.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, PR China. zhanpeng1982@163.com
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D021581:Active Transport, Cell Nucleus; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism*; D055808:Drug Discovery; D019427:HIV Integrase / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D011485:Protein Binding; D028901:alpha Karyopherins / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D036341:Intercellular Signaling Peptides and Proteins; D028901:alpha Karyopherins; C119380:lens epithelium-derived growth factor; D054325:vpr Gene Products, Human Immunodeficiency Virus; D019427:HIV Integrase