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Sargassum fusiforme fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase

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...

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Autores principales: Paskaleva, Elena E, Lin, Xudong, Duus, Karen, McSharry, James J, Veille, Jean-Claude L, Thornber, Carol, Liu, Yanze, Lee, David Yu-Wei, Canki, Mario
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267448/
https://www.ncbi.nlm.nih.gov/pubmed/18197976
http://dx.doi.org/10.1186/1743-422X-5-8
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author Paskaleva, Elena E
Lin, Xudong
Duus, Karen
McSharry, James J
Veille, Jean-Claude L
Thornber, Carol
Liu, Yanze
Lee, David Yu-Wei
Canki, Mario
author_facet Paskaleva, Elena E
Lin, Xudong
Duus, Karen
McSharry, James J
Veille, Jean-Claude L
Thornber, Carol
Liu, Yanze
Lee, David Yu-Wei
Canki, Mario
author_sort Paskaleva, Elena E
collection PubMed
description 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 IC(50 )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.
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spelling pubmed-22674482008-03-14 Sargassum fusiforme fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase Paskaleva, Elena E Lin, Xudong Duus, Karen McSharry, James J Veille, Jean-Claude L Thornber, Carol Liu, Yanze Lee, David Yu-Wei Canki, Mario Virol J Research 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 IC(50 )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. BioMed Central 2008-01-15 /pmc/articles/PMC2267448/ /pubmed/18197976 http://dx.doi.org/10.1186/1743-422X-5-8 Text en Copyright © 2008 Paskaleva et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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.
spellingShingle Research
Paskaleva, Elena E
Lin, Xudong
Duus, Karen
McSharry, James J
Veille, Jean-Claude L
Thornber, Carol
Liu, Yanze
Lee, David Yu-Wei
Canki, Mario
Sargassum fusiforme fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase
title Sargassum fusiforme fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase
title_full Sargassum fusiforme fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase
title_fullStr Sargassum fusiforme fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase
title_full_unstemmed Sargassum fusiforme fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase
title_short Sargassum fusiforme fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase
title_sort sargassum fusiforme fraction is a potent and specific inhibitor of hiv-1 fusion and reverse transcriptase
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267448/
https://www.ncbi.nlm.nih.gov/pubmed/18197976
http://dx.doi.org/10.1186/1743-422X-5-8
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