Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: Part II. Integrase inhibition

Sylvia Lee-Huang, Philip Lin Huang, Dawei Zhang, Jae Wook Lee, Ju Bao, Yongtao Sun, Young Tae Chang, John Zhang, Paul Lee Huang

Research output: Contribution to journalArticle


We report molecular modeling and functional confirmation of Ole and HT binding to HIV-1 integrase. Docking simulations identified two binding regions for Ole within the integrase active site. Region I encompasses the conserved D64-D116-E152 motif, while region II involves the flexible loop region formed by amino acid residues 140-149. HT, on the other hand, binds to region II. Both Ole and HT exhibit favorable interactions with important amino acid residues through strong H-bonding and van der Waals contacts, predicting integrase inhibition. To test and confirm modeling predictions, we examined the effect of Ole and HT on HIV-1 integrase activities including 3′-processing, strand transfer, and disintegration. Ole and HT exhibit dose-dependent inhibition on all three activities, with EC50 s in the nanomolar range. These studies demonstrate that molecular modeling of target-ligand interaction coupled with structural-activity analysis should facilitate the design and identification of innovative integrase inhibitors and other therapeutics.

Original languageEnglish (US)
Pages (from-to)879-884
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - Mar 23 2007



  • AIDS
  • HIV-1
  • HIV-1 integrase inhibitor
  • Hydroxytyrosol (HT)
  • Molecular modeling
  • Natural product
  • Oleuropein (Ole)
  • Olive leaf extract (OLE)
  • Small molecule HIV-1 inhibitors
  • Structure-function

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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