Selective in vitro protection of SIVagm-induced cytolysis by ajoene, [(E)-(Z)-4,5,9-trithiadodeca-1,6,11-triene-9 oxide]

Biomed Pharmacother. 1998;52(5):229-35. doi: 10.1016/S0753-3322(98)80021-8.

Abstract

We studied the effect of synthetic ajoene on simian immunodeficiency virus (SIVagm)-mediated cell fusion and subsequent virus-induced cytolysis. Our data indicate that this compound is a strong antifusion agent with a 50% syncytium inhibitory concentration (SIC50%) value of about 2.9 microM. We suggest that ajoene interacts with the cell-specific integrin molecules and sterically hinders the association between fusion (or other co-receptors) and the CD4-gp120 complex at the cell surface of SIV-infected cells. Although ajoene was maximally effective in suppressing syncytium formation during the early period (ie, up to 6 h) of the fusion process, when the compound was recurrently added to the co-cultures, the inhibitory effect was regained and further cell death was markedly delayed. This indicates that ajoene was also effective after the initial cell-to-cell contact stage. These data suggest that ajoene may be a promising approach for the treatment of SIV/human immunodeficiency virus (HIV) infections.

Publication types

  • Comment

MeSH terms

  • Antiviral Agents / pharmacology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / physiology
  • CD4-Positive T-Lymphocytes / virology
  • Cell Fusion
  • Cell Survival / drug effects*
  • Disulfides / pharmacology*
  • Dose-Response Relationship, Drug
  • Giant Cells / drug effects*
  • Humans
  • Jurkat Cells
  • Kinetics
  • Plant Extracts / pharmacology*
  • Simian Immunodeficiency Virus / drug effects
  • Simian Immunodeficiency Virus / pathogenicity*
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Antiviral Agents
  • Disulfides
  • Plant Extracts
  • ajoene