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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following attachment and entry of human immunodeficiency virus (HIV) into a host cell, the HIV genomic RNA is reverse transcribed to cDNA. This step may be inhibited by hypericin, a compound that induces alterations of the retroviral capsid. Incubation of HIV with hypericin rendered the virus noninfectious. The replication of HIV was blocked early; HIV cDNA could not be detected in cells challenged with hypericin-treated HIV. Hypericin did not inhibit the binding of recombinant gp120 to CD4+ cells, nor did hypericin inhibit syncytium formation. However, reverse transcriptase activity could not be released from hypericin-treated virions. Western blot analysis revealed altered mobility of the HIV major capsid protein (p24) following hypericin treatment. Hypericin-treated recombinant HIV p24 exhibited similar altered mobility. The inactivation of HIV infectivity and the alterations in p24 mobility required hypericin incubations in the presence of visible light. Collectively, these data suggest that photochemical alterations of the HIV capsid may contribute to the hypericin-mediated inactivation of HIV. Such alterations may inhibit the release of RT activity from treated HIV, and prevent uncoating and subsequent reverse transcription of the HIV genome within a target cell.
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PMID:Inactivation of the human immunodeficiency virus by hypericin: evidence for photochemical alterations of p24 and a block in uncoating. 128 9

Extracts of Homalanthus nutans, a plant used in Samoan herbal medicine, exhibited potent activity in an in vitro, tetrazolium-based assay which detects the inhibition of the cytopathic effects of human immunodeficiency virus (HIV-1). The active constituent was identified as prostratin, a relatively polar 12-deoxyphorbol ester. Noncytotoxic concentrations of prostratin from greater than or equal to 0.1 to greater than 25 microM protected T-lymphoblastoid CEM-SS and C-8166 cells from the killing effects of HIV-1. Cytoprotective concentrations of prostratin greater than or equal to 1 microM essentially stopped virus reproduction in these cell lines, as well as in the human monocytic cell line U937 and in freshly isolated human monocyte/macrophage cultures. Prostratin bound to and activated protein kinase C in vitro in CEM-SS cells and elicited other biochemical effects typical of phorbol esters in C3H10T1/2 cells; however, the compound does not appear to be a tumor promoter. In skin of CD-1 mice, high doses of prostratin induced ornithine decarboxylase only to 25-30% of the levels induced by typical phorbol esters at doses 1/30 or less than that used for prostratin, produced kinetics of edema formation characteristic of the nonpromoting 12-deoxyphorbol 13-phenylacetate, and failed to induce the acute or chronic hyperplasias typically caused by tumor-promoting phorbols at doses of 1/100 or less than that used for prostratin.
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PMID:A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1. 159 53

Hypericin, a photodynamic plant quinone, readily inactivated murine cytomegalovirus (MCMV), Sindbis virus, and human immunodeficiency virus type 1 (HIV-1), especially on exposure to fluorescent light. Sindbis virus was significantly more sensitive than MCMV. The inactivated MCMV, when used to infect cells, was incapable of synthesizing early or late viral antigens. In addition to this direct virucidal effect, when hypericin was added to cells infected with viable MCMV, inhibition was also observed, particularly when the compound was added in the first two hours of infection. Again the antiviral effect was augmented by visible light. At effective antiviral concentrations, there were no discernible adverse effects on cultured cells. Thus hypericin appears to have two modes of antiviral activity: one directed at the virions, possibly on membrane components (although other virion targets cannot be ruled out), and the other directed at virus-infected cells. Both activities are substantially enhanced by light. Other recent studies on the antiviral activities of hypericin have not considered the role of light, and it is conceivable that apparent discrepancies between their results may have reflected different conditions of light exposure.
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PMID:Antiviral activities of hypericin. 165 Jan 64

Various anthraquinones substituted with hydroxyl, amino, halogen, carboxylic acid, substituted aromatic group, and sulfonate were tested to determine their activity against human immunodeficiency virus type 1 (HIV-1) in primary human lymphocytes. Among the compounds tested, polyphenolic and/or polysulfonate substituted anthraquinones were found to possess the most potent antiviral activity. Hypericin, an anthraquinone dimer previously shown to have activity against nonhuman retroviruses also exhibited anti-HIV-1 activity in lymphocytes. the active anthraquinones inhibited HIV-1 reverse transcriptase. However, this enzyme inhibition was selective only for 1,2,5,8-tetrahydroanthraquinone and hypericin. Hypericin interacts nonspecifically with protein suggesting that this effect may dictate its inhibitory activity against the viral reverse transcriptase.
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PMID:Anthraquinones as a new class of antiviral agents against human immunodeficiency virus. 169 40

Hypericin and pseudohypericin are naturally occurring polycyclic quinones which have recently been shown to inhibit the infectivity of several retroviruses, including human immunodeficiency virus. To better understand the antiviral mechanisms of these compounds, hypericin and a series of analogous quinones were synthesized and tested for anti-retroviral activity against equine infectious anemia virus (EIAV). Treatment of EIAV-infected cells with hypericin reduced the production of infectious virus by 99.99%. None of the analogs were found to inhibit virus replication. These results suggest that the complete ring structure of hypericin is required, but not sufficient, for antiviral activity.
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PMID:Antiretroviral activity of synthetic hypericin and related analogs. 169 34

Administration of the aromatic polycyclic dione compounds hypericin or pseudohypericin to experimental animals provides protection from disease induced by retroviruses that give rise to acute, as well as slowly progressive, diseases. For example, survival from Friend virus-induced leukemia is significantly prolonged by both compounds, with hypericin showing the greater potency. Viremia induced by LP-BM5 murine immunodeficiency virus is markedly suppressed after infrequent dosage of either substance. These compounds affect the retroviral infection and replication cycle at least at two different points: (i) Assembly or processing of intact virions from infected cells was shown to be affected by hypericin. Electron microscopy of hypericin-treated, virus-producing cells revealed the production of particles containing immature or abnormally assembled cores, suggesting the compounds may interfere with processing of gag-encoded precursor polyproteins. The released virions contain no detectable activity of reverse transcriptase. (ii) Hypericin and pseudohypericin also directly inactivate mature and properly assembled retroviruses as determined by assays for reverse transcriptase and infectivity. Accumulating data from our laboratories suggest that these compounds inhibit retroviruses by unconventional mechanisms and that the potential therapeutic value of hypericin and pseudohypericin should be explored in diseases such as AIDS.
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PMID:Studies of the mechanisms of action of the antiretroviral agents hypericin and pseudohypericin. 254 93

Hypericin and pseudohypericin which have been isolated from plants of the Hypericum family are aromatic polycyclic diones. Daniel Meruelo et. al. have reported that hypericin and pseudohypericin showed potent antiretroviral activity including anti-human immunodeficiency virus (1,2). However, the mechanism of these antiretroviral activities has not been clarified. In the course of screening specific inhibitors of protein kinase C we have found that both compounds specifically inhibit protein kinase C with IC50 values 1.7 micrograms/ml and 15 micrograms/ml, respectively, and show antiproliferative activity against mammalian cells. These data suggest that antiretroviral activity of hypericin and pseudohypericin could be attributable to the inhibition of some phosphorylation involved by protein kinase C during viral infection of cells.
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PMID:Hypericin and pseudohypericin specifically inhibit protein kinase C: possible relation to their antiretroviral activity. 255 52

The mechanism of the antiviral activity of hypericin was characterized and compared with that of rose bengal. Both compounds inactivate enveloped (but not unenveloped) viruses upon illumination by visible light. Human immunodeficiency and vesicular stomatitis viruses were photodynamically inactivated by both dyes at nanomolar concentrations. Photodynamic inactivation of fusion (hemolysis) by vesicular stomatitis, influenza, and Sendai viruses was induced by both dyes under similar conditions (e.g., I50 = 20-50 nM for vesicular stomatitis virus), suggesting that loss of infectivity resulted from inactivation of fusion. Syncytium formation, between cells activated to express human immunodeficiency virus gp120 on their surfaces and CD4+ cells, was inhibited by illumination in the presence of 1 microM hypericin. Hypericin and rose bengal thus exert similar virucidal effects. Both presumably act by the same mechanism--namely, the inactivation of the viral fusion function by singlet oxygen produced upon illumination. The implications of this photodynamic antiviral action for the potential therapeutic usefulness of both hypericin and rose bengal are discussed.
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PMID:Photodynamic inactivation of infectivity of human immunodeficiency virus and other enveloped viruses using hypericin and rose bengal: inhibition of fusion and syncytia formation. 767 35

Hypericin, a polycyclic aromatic dione isolated from plants, is presently being clinically evaluated as an antiviral agent in the treatment of human immunodeficiency virus (HIV) infection. In addition, it is known to be a potent protein kinase C inhibitor. To evaluate its potential as an inhibitor of glioma growth, an established (U87) and low-passage glioma line (93-492) were treated with hypericin in tissue culture for a period of 48 hours after passage. Hypericin inhibited the glioma growth in a dose-related manner, with a marked inhibition of growth in the low-micromolar concentration range (e.g., in line U87 and low-passage line 93-492, a concentration of hypericin of 10 mumol/L produced 62 and 76% decreases in [3H]thymidine uptake, respectively). Because the reported inhibitory effects of protein kinase C are enhanced by visible light, [3H]thymidine uptake was measured in both the presence and the absence of visible light. In glioma line A172, the presence of light slightly increased the inhibitory effect of hypericin. Moreover, an apoptosis (i.e., programmed cell death) assay was performed to determine whether the treatment of glioma cells with hypericin was cytostatic or cytocidal. Cells were harvested, and purified deoxyribonucleic acid (DNA) was analyzed by agarose gel electrophoresis. DNA from cells treated with hypericin for 48 hours exhibited a classical "ladder" pattern of oligonucleosome-sized fragments characteristic of apoptosis. These data suggest that the proven safe drug hypericin may have potential as an antiglioma agent; we suggest clinical trials.
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PMID:Hypericin: a potential antiglioma therapy. 780 14

Hypericin is a naturally occurring photosensitizer that displays potent antiviral activity in the presence of light. The absence of light in many regions of the body may preclude the use of hypericin and other photosensitizers as therapeutic compounds for the treatment of viral infections in vivo. The chemiluminescent oxidation of luciferin by the luciferase from the North American firefly Photinus pyralis was found to generate sufficiently intense and long-lived emission to induce antiviral activity of hypericin. Light-induced virucidal activity of hypericin was demonstrated against equine infectious anemia virus, a lentivirus structurally, genetically, and antigenically related to the human immunodeficiency virus. The implications for exploiting chemiluminescence as a "molecular flashlight" for effecting photodynamic therapy against virus-infected cells and tumor cells are discussed.
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PMID:Chemiluminescent activation of the antiviral activity of hypericin: a molecular flashlight. 799 18


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