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Copyright © 2008 Paskaleva et al; licensee BioMed Central Ltd. Sargassum fusiforme fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase Elena E Paskaleva,1 Xudong Lin,1 Karen Duus,1 James J McSharry,2 Jean-Claude L Veille,1,3 Carol Thornber,4 Yanze Liu,5 David Yu-Wei Lee,5 and Mario Canki  11Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY, USA 2Ordway Research Institute, Inc., Albany, NY, USA 3Department of Ob/Gyn, Albany Medical College, Albany, NY, USA 4Department of Biological Sciences, University of Rhode Island, Kingston, USA 5Mailman Research Center, McLean Hospital, Harvard Medical School, Belmont, MA, USA Corresponding author.Elena E Paskaleva: paskale/at/mail.amc.edu; Xudong Lin: linx/at/mail.amc.edu; Karen Duus: duusk/at/mail.amc.edu; James J McSharry: jmcsharry/at/ordwayreseach.org; Jean-Claude L Veille: veillej/at/mail.amc.edu; Carol Thornber: thornber/at/uri.edu; Yanze Liu: yliu/at/mclean.harvard.edu; David Yu-Wei Lee: dlee/at/mclean.harvard.edu; Mario Canki: cankim/at/mail.amc.edu Received October 27, 2007; Accepted January 15, 2008. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | ||||
Abstract Sargassum fusiforme (Harvey) Setchell has been shown to be a highly effective inhibitor of HIV-1 infection. To identify its mechanism of action, we performed bioactivity-guided fractionation on Sargassum fusiforme mixture. Here, we report isolation of a bioactive fraction SP4-2 (S. fusiforme), which at 8 μg/ml inhibited HIV-1 infection by 86.9%, with IC50 value of 3.7 μg. That represents 230-fold enhancement of antiretroviral potency as compared to the whole extract. Inhibition was mediated against both CXCR4 (X4) and CCR5 (R5) tropic HIV-1. Specifically, 10 μg/ml SP4-2 blocked HIV-1 fusion and entry by 53%. This effect was reversed by interaction of SP4-2 with sCD4, suggesting that S. fusiforme inhibits HIV-1 infection by blocking CD4 receptor, which also explained observed inhibition of both X4 and R5-tropic HIV-1. SP4-2 also inhibited HIV-1 replication after virus entry, by directly inhibiting HIV-1 reverse transcriptase (RT) in a dose dependent manner by up to 79%. We conclude that the SP4-2 fraction contains at least two distinct and biologically active molecules, one that inhibits HIV-1 fusion by interacting with CD4 receptor, and another that directly inhibits HIV-1 RT. We propose that S. fusiforme is a lead candidate for anti-HIV-1 drug development. | ||||
