Ginkgolic acid inhibits HIV protease activity and HIV infection in vitro

Jian Ming Lü, Shaoyu Yan, Saha Jamaluddin, Sarah M. Weakley, Zhengdong Liang, Edward B. Siwak, Qizhi Yao, Changyi Chen

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Background: Several HIV protease mutations, which are resistant to clinical HIV protease inhibitors (PIs), have been identified. There is a great need for second-generation PIs with different chemical structures and/or with an alternative mode of inhibition. Ginkgolic acid is a natural herbal substance and a major component of the lipid fraction in the nutshells of the Ginkgo biloba tree. The objective of this study was to determine whether ginkgolic acid could inhibit HIV protease activity in a cell free system and HIV infection in human cells. Material/Methods: Purified ginkgolic acid and recombinant HIV-1 HXB2 KIIA protease were used for the HIV protease activity assay. Human peripheral blood mononuclear cells (PBMCs) were used for HIV infection (HIV-1SF162 virus), determined by a p24gag ELISA. Cytotoxicity was also determined. Results: Ginkgolic acid (31.2 μg/ml) inhibited HIV protease activity by 60%, compared with the negative control, and the effect was concentration-dependent. In addition, ginkgolic acid treatment (50 and 100 μg/ml) effectively inhibited the HIV infection at day 7 in a concentration-dependent manner. Ginkgolic acid at a concentration of up to 150 μg/ml demonstrated very limited cytotoxicity. Conclusions: Ginkgolic acid effectively inhibits HIV protease activity in a cell free system and HIV infection in PBMCs without significant cytotoxicity. Ginkgolic acid may inhibit HIV protease through different mechanisms than current FDA-approved HIV PI drugs. These properties of ginkgolic acid make it a promising therapy for HIV infection, especially as the clinical problem of viral resistance to HIV PIs continues to grow.

Original languageEnglish (US)
Pages (from-to)BR293-BR298
JournalMedical Science Monitor
Volume18
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Cytotoxicity
  • Ginkgolic acid
  • HIV infection
  • HIV protease inhibitor

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Lü, J. M., Yan, S., Jamaluddin, S., Weakley, S. M., Liang, Z., Siwak, E. B., Yao, Q., & Chen, C. (2012). Ginkgolic acid inhibits HIV protease activity and HIV infection in vitro. Medical Science Monitor, 18(8), BR293-BR298. https://doi.org/10.12659/MSM.883261