1. Sargassum fusiforme fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase.
- Author
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Paskaleva EE, Lin X, Duus K, McSharry JJ, Veille JC, Thornber C, Liu Y, Lee DY, and Canki M
- Subjects
- Anti-HIV Agents pharmacology, CD4 Antigens drug effects, CD4 Antigens metabolism, Cell Line, Dose-Response Relationship, Drug, Enzyme Inhibitors, HIV Infections metabolism, HIV Reverse Transcriptase antagonists & inhibitors, HIV-1 physiology, Humans, Receptors, CCR5 metabolism, Receptors, CXCR4 metabolism, Receptors, Virus metabolism, Virus Attachment drug effects, Virus Internalization drug effects, Biological Products pharmacology, HIV Infections virology, HIV-1 drug effects, Sargassum
- 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 mug/ml inhibited HIV-1 infection by 86.9%, with IC50 value of 3.7 mug. 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 mug/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.
- Published
- 2008
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