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 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.
Paskaleva
Elena E
EE
Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY, USA. paskale@mail.amc.edu
Lin
Xudong
X
Duus
Karen
K
McSharry
James J
JJ
Veille
Jean-Claude L
JC
Thornber
Carol
C
Liu
Yanze
Y
Lee
David Yu-Wei
DY
Canki
Mario
M
D019380:Anti-HIV Agents / Q000494:pharmacology; D001688:Biological Products / Q000494:pharmacology*; D015704:CD4 Antigens / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D015658:HIV Infections / Q000378:metabolism / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D044647:Sargassum; D053585:Virus Attachment / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects
D019380:Anti-HIV Agents; D001688:Biological Products; D015704:CD4 Antigens; D004791:Enzyme Inhibitors; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011991:Receptors, Virus; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase