The carotenoid halocynthiaxanthin: a novel inhibitor of the reverse transcriptases of human immunodeficiency viruses type 1 and type 2.
We have studied the effects of a natural carotenoid, identified as halocynthiaxanthin, on the enzymatic activities associated with the recombinant preparations of the reverse transcriptases (RTs) of human immunodeficiency viruses (HIV) types 1 and 2. The carotenoid was found to be a potent inhibitor of the RNA-dependent DNA polymerase activity (with 50% inhibition obtained at 5-7 microM halocynthiaxanthin), whereas the DNA-dependent DNA polymerase function of both RTs was significantly less sensitive to the inhibitor. Conversely, the ribonuclease H activity associated with the two HIV RTs was essentially insensitive to the carotenoid. The RNA-dependent DNA polymerase function of RT is the only unique activity found in this enzyme that is not expressed at significant levels in uninfected eukaryotic cells. Therefore, it is possible that this carotenoid may serve as a good candidate for the development of novel potent and specific inhibitors of HIV RT.
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
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Loya
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Kashman
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Hizi
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002338:Carotenoids / Q000302:isolation & purification / Q000494:pharmacology*; D002384:Catalysis; D002417:Cattle; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D015498:HIV-2 / Q000187:drug effects* / Q000201:enzymology; D011161:Porifera / Q000737:chemistry; D012194:RNA-Directed DNA Polymerase; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D018894:Reverse Transcriptase Inhibitors; D013950:Thymus Gland / Q000201:enzymology; D024341:Xanthophylls
D000998:Antiviral Agents; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D024341:Xanthophylls; D002338:Carotenoids; C073045:halocynthiaxanthin; C072416:reverse transcriptase, Human immunodeficiency virus 2; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase