Computational study of bindings of olive leaf extract (OLE) to HIV-1 fusion protein gp41

FEBS Lett. 2007 Jun 12;581(14):2737-42. doi: 10.1016/j.febslet.2007.05.029. Epub 2007 May 21.


Recent experimental study found that OLE (olive leaf extract) has anti-HIV activity by blocking the HIV virus entry to host cells [Lee-Huang, S., Zhang, L., Huang, P.L., Chang, Y. and Huang, P.L. (2003) Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem. Biophys. Res. Commun. 307, 1029; Lee-Huang, S., Huang, P.L., Zhang, D., Lee, J.W., Bao, J., Sun, Y., Chang, Y.-Tae, Zhang, J.Z.H. and Huang, P.L. (2007) Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol. Biochem. Biophys. Res. Commun. 354, 872-878, 879-884]. As part of a joint experimental and theoretical effort, we report here computational study to help identify and characterize the binding complexes of several main compounds of OLE (olive leaf extract) to HIV-1 envelop protein gp41. A number of possible binding modes are found by docking oleuropein and its metabolites, aglycone, elenolic acid and hydroxytyrosol, onto the hydrophobic pocket on gp41. Detailed OLE-gp41 binding interactions and free energies of binding are obtained through molecular dynamics simulation and MM-PBSA calculation. Specific molecular interactions in our predicted OLE/gp41 complexes are identified and hydroxytyrosol is identified to be the main moiety for binding to gp41. This computational study complements the corresponding experimental investigation and helps establish a good starting point for further refinement of OLE-based gp41 inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology
  • Computer Simulation*
  • HIV Envelope Protein gp41 / chemistry*
  • HIV Envelope Protein gp41 / metabolism
  • HIV-1 / chemistry
  • HIV-1 / drug effects
  • Humans
  • Hydrogen Bonding
  • Iridoids
  • Models, Molecular
  • Molecular Structure
  • Olea / chemistry*
  • Phenylethyl Alcohol / analogs & derivatives
  • Phenylethyl Alcohol / chemistry
  • Phenylethyl Alcohol / metabolism
  • Phenylethyl Alcohol / pharmacology
  • Plant Extracts / chemistry*
  • Plant Extracts / metabolism
  • Plant Extracts / pharmacology
  • Plant Leaves / chemistry*
  • Protein Binding
  • Pyrans / chemistry
  • Pyrans / metabolism
  • Pyrans / pharmacology
  • Thermodynamics


  • Antiviral Agents
  • HIV Envelope Protein gp41
  • Iridoids
  • Plant Extracts
  • Pyrans
  • 3,4-dihydroxyphenylethanol
  • oleuropein
  • elenolic acid
  • Phenylethyl Alcohol