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

Abstract

We have identified oleuropein (Ole) and hydroxytyrosol (HT) as a unique class of HIV-1 inhibitors from olive leaf extracts effective against viral fusion and integration. We used molecular docking simulation to study the interactions of Ole and HT with viral targets. We find that Ole and HT bind to the conserved hydrophobic pocket on the surface of the HIV-gp41 fusion domain by hydrogen bonds with Q577 and hydrophobic interactions with I573, G572, and L568 on the gp41 N-terminal heptad repeat peptide N36, interfering with formation of the gp41 fusion-active core. To test and confirm modeling predications, we examined the effect of Ole and HT on HIV-1 fusion complex formation using native polyacrylamide gel electrophoresis and circular dichroism spectroscopy. Ole and HT exhibit dose-dependent inhibition on HIV-1 fusion core formation with EC50s of 66-58 nM, with no detectable toxicity. Our findings on effects of HIV-1 integrase are reported in the subsequent article.

Original languageEnglish (US)
Pages (from-to)872-878
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume354
Issue number4
DOIs
StatePublished - Mar 23 2007

Fingerprint

HIV Fusion Inhibitors
HIV Integrase Inhibitors
Integrase Inhibitors
Integrases
Fusion reactions
Molecules
HIV-1
HIV Envelope Protein gp41
Molecular Docking Simulation
Virus Integration
Circular dichroism spectroscopy
Native Polyacrylamide Gel Electrophoresis
Terminal Repeat Sequences
Olea
Circular Dichroism
Electrophoresis
Hydrophobic and Hydrophilic Interactions
Toxicity
Hydrogen
Spectrum Analysis

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol : Part I. Integrase inhibition. / Lee-Huang, Sylvia; Huang, Philip Lin; Zhang, Dawei; Lee, Jae Wook; Bao, Ju; Sun, Yongtao; Chang, Young Tae; Zhang, John; Huang, Paul Lee.

In: Biochemical and Biophysical Research Communications, Vol. 354, No. 4, 23.03.2007, p. 872-878.

Research output: Contribution to journalArticle

Lee-Huang, Sylvia ; Huang, Philip Lin ; Zhang, Dawei ; Lee, Jae Wook ; Bao, Ju ; Sun, Yongtao ; Chang, Young Tae ; Zhang, John ; Huang, Paul Lee. / Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol : Part I. Integrase inhibition. In: Biochemical and Biophysical Research Communications. 2007 ; Vol. 354, No. 4. pp. 872-878.
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