<it>Sargassum fusiforme </it>fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase
<p>Abstract</p> <p><it>Sargassum fusiforme </it>(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 <it>Sargassum fusiforme </it>mixture...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2008-01-01
|
| Series: | Virology Journal |
| Online Access: | http://www.virologyj.com/content/5/1/8 |
| _version_ | 1828221442130444288 |
|---|---|
| author | Thornber Carol Veille Jean-Claude L McSharry James J Duus Karen Lin Xudong Paskaleva Elena E Liu Yanze Lee David Canki Mario |
| author_facet | Thornber Carol Veille Jean-Claude L McSharry James J Duus Karen Lin Xudong Paskaleva Elena E Liu Yanze Lee David Canki Mario |
| author_sort | Thornber Carol |
| collection | DOAJ |
| description | <p>Abstract</p> <p><it>Sargassum fusiforme </it>(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 <it>Sargassum fusiforme </it>mixture. Here, we report isolation of a bioactive fraction SP4-2 (<it>S. fusiforme</it>), which at 8 μg/ml inhibited HIV-1 infection by 86.9%, with IC<sub>50 </sub>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 <it>S. fusiforme </it>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 <it>S. fusiforme </it>is a lead candidate for anti-HIV-1 drug development.</p> |
| first_indexed | 2024-04-12T16:41:04Z |
| format | Article |
| id | doaj.art-18cd1df1c35e42ddb4938b3833307cd2 |
| institution | Directory Open Access Journal |
| issn | 1743-422X |
| language | English |
| last_indexed | 2024-04-12T16:41:04Z |
| publishDate | 2008-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj.art-18cd1df1c35e42ddb4938b3833307cd22022-12-22T03:24:47ZengBMCVirology Journal1743-422X2008-01-0151810.1186/1743-422X-5-8<it>Sargassum fusiforme </it>fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptaseThornber CarolVeille Jean-Claude LMcSharry James JDuus KarenLin XudongPaskaleva Elena ELiu YanzeLee DavidCanki Mario<p>Abstract</p> <p><it>Sargassum fusiforme </it>(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 <it>Sargassum fusiforme </it>mixture. Here, we report isolation of a bioactive fraction SP4-2 (<it>S. fusiforme</it>), which at 8 μg/ml inhibited HIV-1 infection by 86.9%, with IC<sub>50 </sub>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 <it>S. fusiforme </it>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 <it>S. fusiforme </it>is a lead candidate for anti-HIV-1 drug development.</p>http://www.virologyj.com/content/5/1/8 |
| spellingShingle | Thornber Carol Veille Jean-Claude L McSharry James J Duus Karen Lin Xudong Paskaleva Elena E Liu Yanze Lee David Canki Mario <it>Sargassum fusiforme </it>fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase Virology Journal |
| title | <it>Sargassum fusiforme </it>fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase |
| title_full | <it>Sargassum fusiforme </it>fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase |
| title_fullStr | <it>Sargassum fusiforme </it>fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase |
| title_full_unstemmed | <it>Sargassum fusiforme </it>fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase |
| title_short | <it>Sargassum fusiforme </it>fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase |
| title_sort | it sargassum fusiforme it fraction is a potent and specific inhibitor of hiv 1 fusion and reverse transcriptase |
| url | http://www.virologyj.com/content/5/1/8 |
| work_keys_str_mv | AT thornbercarol itsargassumfusiformeitfractionisapotentandspecificinhibitorofhiv1fusionandreversetranscriptase AT veillejeanclaudel itsargassumfusiformeitfractionisapotentandspecificinhibitorofhiv1fusionandreversetranscriptase AT mcsharryjamesj itsargassumfusiformeitfractionisapotentandspecificinhibitorofhiv1fusionandreversetranscriptase AT duuskaren itsargassumfusiformeitfractionisapotentandspecificinhibitorofhiv1fusionandreversetranscriptase AT linxudong itsargassumfusiformeitfractionisapotentandspecificinhibitorofhiv1fusionandreversetranscriptase AT paskalevaelenae itsargassumfusiformeitfractionisapotentandspecificinhibitorofhiv1fusionandreversetranscriptase AT liuyanze itsargassumfusiformeitfractionisapotentandspecificinhibitorofhiv1fusionandreversetranscriptase AT leedavid itsargassumfusiformeitfractionisapotentandspecificinhibitorofhiv1fusionandreversetranscriptase AT cankimario itsargassumfusiformeitfractionisapotentandspecificinhibitorofhiv1fusionandreversetranscriptase |