title: Cell-based chemical genetic screen identifies damnacanthal as an inhibitor of HIV-1 Vpr induced cell death.
abstract: Viral protein R (Vpr), one of the human immunodeficiency virus type 1 (HIV-1) accessory proteins, contributes to multiple cytopathic effects, G2 cell cycle arrest and apoptosis. The mechanisms of Vpr have been intensely studied because it is believed that they underlie HIV-1 pathogenesis. We here report a cell-based small molecule screen on Vpr induced cell death in the context of HIV-1 infection. From the screen of 504 bioactive compounds, we identified damnacanthal (Dam), a component of noni [corrected] as an inhibitor of Vpr induced cell death. Our studies illustrate a novel efficient platform for drug discovery and development in anti-HIV therapy which should also be applicable to other viruses.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. masa3k@ucla.edu
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kamata
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Wu
authors.forename: Dong Sung
authors.initials: DS
authors.lastname: An
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Saxe
authors.forename: Robert
authors.initials: R
authors.lastname: Damoiseaux
authors.forename: Michael E
authors.initials: ME
authors.lastname: Phelps
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Irvin S Y
authors.initials: IS
authors.lastname: Chen
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D016195:G2 Phase / Q000187:drug effects / Q000235:genetics; D016336:Gene Products, vpr / Q000037:antagonists & inhibitors* / Q000502:physiology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D010641:Phenotype; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D000880:Anthraquinones; D019380:Anti-HIV Agents; D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus; C079170:damnacanthal