Screening For Small Molecule Inhibitors Of HIV-1 VPR: Discovery Of Vipirinin And Its Use As A Bioprobe

• Main Author: Ong , Eugene Boon Beng
• Format: Thesis
• Language: English
• Published: 2011
• Subjects: QH1 Natural history (General - Including nature conservation, geographical distribution)
• Online Access: http://eprints.usm.my/41785/1/EUGENE_ONG_BOON_BENG.pdf; http://eprints.usm.my/41785/

The human immunodeficiency virus 1 (HIV-1) viral protein R (Vpr) is an accessory protein that has been known to have multiple roles in HIV-1 pathogenesis. Here, a high-throughput screening (HTS) system was developed to screen chemical libraries in RIKEN Natural Products Depository (NPDepo). Through HTS, NPD4456, a 3-phenyl coumarin based compound, was identified to be an inhibitor of the cell cycle arrest activity of Vpr in yeast. The minimal pharmacophore of the inhibitor was determined through a structure-activity relationship study and more potent derivatives were produced.