Vipirinin, a coumarin-based HIV-1 Vpr inhibitor, interacts with a hydrophobic region of Vpr

Eugene Boon Beng Ong, Nobumoto Watanabe*, Akiko Saito, Yushi Futamura, Khaled Hussein Abd El Galil, Atsushi Koito, Nazalan Najimudin, Hiroyuki Osada

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)


The human immunodeficiency virus 1 (HIV-1) viral protein R (Vpr) is an accessory protein that has been shown to have multiple roles in HIV-1 pathogenesis. By screening chemical libraries in the RIKEN Natural Products Depository, we identified a 3-phenyl coumarin-based compound that inhibited the cell cycle arrest activity of Vpr in yeast and Vpr-dependent viral infection of human macrophages. We determined its minimal pharmacophore through a structure-activity relationship study and produced more potent derivatives.Wedetected direct binding, and by assaying a panelof Vpr mutants,wefound the hydrophobic region about residues Glu-25 and Gln-65 to be potentially involved in the binding of the inhibitor. Our findings exposed a targeting site on Vpr and delineated a convenient approach to explore other targeting sites on the protein using small molecule inhibitors as bioprobes.

Original languageEnglish
Pages (from-to)14049-14056
Number of pages8
JournalJournal of Biological Chemistry
Issue number16
Publication statusPublished - 2011 Apr 22
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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