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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...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2008
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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. |
format | Text |
id | pubmed-2267448 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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