Identification of light-independent inhibition of human immunodeficiency virus-1 infection through bioguided fractionation of Hypericum perforatum

Wendy Maury, University of Iowa
Jason P. Price, University of Iowa
Melinda A. Brindley, University of Iowa
ChoonSeok Oh, University of Iowa
Jeffrey D. Neighbors, University of Iowa
David F. Wiemer, University of Iowa
Nickolas Wills, Iowa State University
Susan Carpenter, Iowa State University
Cathy Hauck, Iowa State University
Patricia A. Murphy, Iowa State University
Mark P. Widrlechner, Iowa State University
Kathleen Delate, Iowa State University
Ganesh Kumar, Iowa State University
George A. Kraus, Iowa State University
Ludmila Rizshsky, Iowa State University
Basil Nikolau, Iowa State University

This article is from Virology Journal, 2009, 6; 101. Doi: 10.1186/1743-422X-6-101. Posted with permission.

Abstract

Background

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 been investigated.

Results

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 present in that fraction. 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.

Conclusion

Through bioguided fractionation, we have identified that 3-hydroxy lauric acid found in field grown Hypericum perforatumhas anti-HIV activity. This novel anti-HIV activity can be potentially developed into inexpensive therapies, expanding the current arsenal of anti-retroviral agents.