Page Banner

United States Department of Agriculture

Agricultural Research Service

Research Project: CENTER FOR RESEARCH ON BOTANICAL DIETARY SUPPLEMENTS Title: Identification of Light-independent Inhibition of Human Immunodeficiency Virus-1 Infection through Bioguided Fractionation of Hypericum perforatum

Authors
item Maury, Wendy -
item Price, Jason -
item Brindley, Melinda -
item Oh, Choon Seok -
item Neighbors, Jeffrey -
item Wiemer, David -
item Wills, Nikolas -
item Carpenter, Susan -
item Hauck, Cathy -
item Murphy, Patricia -
item Widrlechner, Mark
item Delate, Kathleen -
item Kumar, Ganesh -
item Kraus, George -
item Rizshsky, Ludmila -
item Nikolau, Basil -

Submitted to: Virology Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 23, 2009
Publication Date: July 13, 2009
Repository URL: http://www.virologyj.com/content/pdf/1743-422X-6-101.pdf
Citation: Maury, W., Price, J., Brindley, M., Oh, C., Neighbors, J., Wiemer, D., Wills, N., Carpenter, S., Hauck, C., Murphy, P., Widrlechner, M.P., Delate, K., Kumar, G., Kraus, G.A., Rizshsky, L., Nikolau, B. 2009. Identification of Light-independent Inhibition of Human Immunodeficiency Virus-1 Infection through Bioguided Fractionation of Hypericum perforatum. Virology Journal. 6:101. doi:10.1186/1743-422X-6-101. Available: http://www.virologyj.com/content/pdf/1743-422X-6-101.pdf.

Interpretive Summary: Extracts of St. John's Wort (Hypericum perforatum) are known to contain antiviral compounds that are activated by light. In contrast, there are no reports of antiviral effects in St. John's Wort that work in the dark. In this study, we found that purified fractions of chloroform extracts of St. John's Wort inhibited human immunodeficiency virus-1 (HIV-1) in the absence of light. The initial extracts had the desired antiviral properties but were also toxic to the cells being tested. However, we were able to separate the antiviral effects from this undesirable toxicity. Antiviral compounds that had been previously identified have all been toxic. Chemical analyses of our two most active fractions identified the most common components as modified fatty acids, 3-hydroxy lauric acid and 3-hydroxy myristic acid. Synthetic 3-hydroxy lauric acid inhibited HIV infection without cellular toxicity, suggesting that this modified fatty acid is likely responsible for the observed antiviral effects. Production of these modified fatty acids is known to occur in bacteria, but production by plants remains controversial, so we grew St. John's Wort seedlings under sterile conditions. Small quantities of similar modified fatty acids were detected in sterile plants. These novel anti-HIV compounds can be potentially developed into inexpensive therapies, expanding the current arsenal in the fight against AIDS. These findings will likely be of direct use by researchers studying the vulnerabilities of HIV and similar viruses and as a guide to future drug development.

Technical Abstract: Light-dependent activities against enveloped viruses in St. John's Wort (Hypericum perforatum) extracts have been extensively studied. In contrast, light-independent antiviral activity from this species has not. Here, we identify the light-independent inhibition of human immunodeficiency virus-1 (HIV-1) by highly purified fractions of chloroform extracts of H. perforatum. Both cytotoxicity and antiviral activity were evident in initial chloroform extracts, but bioassay-guided fractionation produced fractions that inhibited HIV-1 with little to no cytotoxicity. Separation of these two biological activities has not been reported for constituents responsible for the light-dependent antiviral activities. Antiviral activity was associated with more polar subfractions. GC/MS analysis of the two most active subfractions identified 3-hydroxy lauric acid as predominant in one fraction and 3-hydroxy myristic acid as predominant in the other. Synthetic 3-hydroxy lauric acid inhibited HIV infectivity without cytotoxicity, suggesting that this modified fatty acid is likely responsible for observed antiviral activity. As production of 3-hydroxy fatty acids by plants remains controversial, H. perforatum seedlings were grown sterilely and evaluated for presence of 3-hydroxy fatty acids by GC/MS. Small quantities of some 3-hydroxy fatty acids were detected in sterile plants, whereas different 3-hydroxy fatty acids were detected in our chloroform extracts or field-grown material. Novel anti-HIV activity identified through this bioactivity-guided fractionation can be potentially developed into inexpensive therapies, expanding the current arsenal of anti-retroviral agents.

Last Modified: 10/21/2014
Footer Content Back to Top of Page