Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Keggin polyoxotungstate PM-19 K7[PTi2W10O40].6H2O was found to be a potent inhibitor of the replication of human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), in OKT4+ cells. In contrast, the effect of HPA 23 (NH4)17Na[NaSb9W21O86], an inhibitor of reverse transcriptase of HIV, was not significant.
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PMID:Inhibition of replication of human immunodeficiency virus by a heteropolyoxotungstate (PM-19). 233 49

This article outlines steps in the development of antiviral drugs, with particular emphasis on therapeutic regimens for infections with human T-lymphotropic virus type III (HTLV-III). Inhibitors of reverse transcriptase activity, including suramin, antimoniotungstate (HPA-23), and trisodium phosphonorformate have shown in vitro activity against HTLV-III in early clinical trials. Other significant antiviral agents are recombinant interferon alpha-A, ribavirin, and ansamycin. Recent evidence suggests that antibodies to envelope protein, gp120, may be essential for neutralization. Combinations of antiviral agents may prove additive or synergistic, eg, interferons plus reverse transcriptase inhibitors or interferons plus ribavirin. Alternating, sequential antiviral regimens may be useful in reducing resistance and toxicity. However, antiviral agents will not be effective without additonal immunostimulatory therapy for viral control and immune reconstitution.
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PMID:Prospects of therapy for infections with human T-lymphotropic virus type III. 241 93

Suramin and various other selected compounds were evaluated for their in vitro inhibitory effects on the infectivity and replication of human T-cell lymphotropic virus (HTLV/III)/lymphadenopathy-associated virus (LAV). As parameters for infectivity and replication, respectively, we followed the cytopathic effect of HTLV-III/LAV on ATH 8 cells, a T-cell clone with high susceptibility to HTLV-III/LAV, and the expression of HTLV-III/LAV p24 gag protein in H9 cells infected with HTLV-III/LAV. As the most effective inhibitors of HTLV-III/LAV the following substances emerged (in order of decreasing activity): Evans Blue approximately equal to suramin greater than phosphonoformic acid greater than Direct Yellow 50. Several purine nucleoside analogues including vidarabine, tubercidin, neplanocin A, dihydroxypropyladenine, pyrazofurin and ribavirin were not inhibitory to HTLV-III/LAV. In our test systems, involving a high multiplicity of infection, HPA-23, previously reported to be effective against LAV reverse transcriptase, showed no inhibitory effect on HTLV-III/LAV infectivity for ATH 8 cells and proved only weakly inhibitory to HTLV-III/LAV replication in H9 cells. Thus, among the anionic dyes that are structurally related to suramin, compounds were found which were as active as suramin itself, if not more so.
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PMID:Comparative inhibitory effects of suramin and other selected compounds on the infectivity and replication of human T-cell lymphotropic virus (HTLV-III)/lymphadenopathy-associated virus (LAV). 241 66

HPA-23 was used in a parallel, multiple dose study in patients with Centers for Disease Control (CDC)-defined AIDS. Sixteen patients were divided into four dosage groups, receiving 0.25, 0.5, 1.0, or 2.0 mg/kg HPA-23 respectively, by rapid IV infusion five days/week for eight weeks. Blood was collected before, at weeks 1, 3, and 7 of treatment, and two weeks post-therapy. Patient peripheral blood lymphocytes (PBL) were cultivated in the presence of fresh PBL from a healthy donor for 30 days. Media were changed and reverse transcriptase activity (RTA) was tested every four to five days. The results showed a significant decrease in RTA in patients treated with a dose of 0.5 or 1 mg/kg, but only a slight decrease in patients who received the lowest dose. In the group treated with the 2 mg/kg dose, two patients had toxic reactions and were discontinued; the other two showed a slight decrease in RTA. In 40% of treated patients, RTA did not increase again two weeks after the end of treatment. No significant immunologic and clinical changes were noticed during the observation period. In vitro experiments of Con A stimulated PBL in presence and absence of HPA-23 showed an increase in proliferation in the presence of the drug.
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PMID:Reverse transcriptase activity (RTA) in lymphocyte cultures of AIDS patients treated with HPA-23. 243 15

Protein extracts from the protozoan ciliate Paramecium tetraurelia revealed high levels of RNA-dependent DNA polymerase activity (reverse transcriptase). Stable and constant during the somatic phase of the cell cycle, the reverse transcriptase activity quickly diminished following the completion of the sexual phases of the cell cycle: conjugation and autogamy. The Paramecium reverse transcriptase presented a number of common features with retroviral polymerases: ability to copy synthetic templates such as poly(rCm).oligo(dG) as well as mRNA; sensitivity to various reverse transcriptase inhibitors such as HPA 23, suramin, phosphonoformate and ethidium bromide; insensitivity to the action of other DNA and RNA polymerase inhibitors and, finally, the requirement for divalent cations before the enzyme can function: either magnesium or manganese. Although the reverse transcriptase activity was not proven to be independent from one of the DNA polymerases in paramecia, its high activity predicts a role in the paramecia cell cycle. From what we are able to conceive today two possible roles could be envisaged. Participation in the anlage macronucleus formation: micronuclear sequences are first transcripted and, after rearrangements of the RNA molecules, these are retrotranscribed into the macronuclear DNA molecules or association with retrotransposons that participate in the movement of certain macronuclear sequences into the germ-line micronucleus.
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PMID:RNA-dependent DNA polymerase activity in Paramecium tetraurelia: what for? 243 48

We associated HPA 23 (inhibitor of the reverse transcriptase) to cyclosporin A (CSA) for two homosexual patients with positive HIV serology, who had a peripheral thrombocytopenia resistant after alone CSA treatment. HPA 23 was given for 15 days at a dose of 4 mg/kg/day in a 24 hours continuous perfusion. The circulating tungsten blood concentration was about 4.4 micrograms/ml (between 3 and 8.4 micrograms/ml). Even if HPA 23 has frequently been responsible of thrombocytopenia at a dose superior than 2 mg/kg/day and in spite of any CSA activity in single treatment, this association shows a significant platelets increase. But thrombocytopenia reappeared a week after the stay of HPA 23 treatment. So, it is possible that HPA 23 might have, at this circulating blood concentration, an antiviral activity in vitro. In this hypothesis there might be a relation between antiviral replication and autoimmune disorders and, at least, CSA might oppose against the thrombocytopenia induced by HPA 23.
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PMID:[Addition of HPA 23 to cyclosporin in the treatment of thrombopenic purpura in HIV-positive subjects]. 244 94

Ammonium tungsto antimoniate (HPA 23) is a potent inhibitor of nucleic acid polymerases and reverse transcriptases of retroviruses. Its in vivo activity as an HIV inhibitor was previously published. However, its clinical use is limited by pharmacological parameters (short half-life and intravenous administration) and significant side effects (thrombocytopenia). In order to evaluate the place of this drug in the therapeutic strategy of HIV-infected patients, we administered 1.5 mg/kg of HPA 23 in 15 infected patients at various stages of the disease twice a day during 14 days. A significant decrease of reverse transcriptase activity (less than 15% of the initial value) was noticed in 13 patients. This activity remained low at least 6 weeks after the end of the treatment in 8 patients. Thrombocytopenia was the only significant side effect reported and was always transient. This study suggests that HPA 23 can be used as an induction treatment in patients infected by HIV. A maintenance treatment has to be defined, as well as the association to other drugs.
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PMID:Reverse transcriptase activity (RTA) in lymphocyte cultures of HIV-infected patients receiving short treatments of HPA 23. A biological evaluation. 245 97

We used purified bovine leukaemia virus (BLV) to test the inhibitory effects of suramin, HPA-23, and 3'-azidothymidine triphosphate (N3dTTP) on the reverse transcriptase activity. The 50% inhibitory concentrations (ID50) of the compounds were determined to be 2.8 mumol/l (suramin), 8.0 mumol/l (HPA-23), and 0.17 mumol/l (N3dTTP). Kinetic analyses of suramin and HPA-23 inhibition are discussed. The observed inhibitory effects emphasize the suitability of BLV as a model virus for investigations of retrovirus chemotherapy.
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PMID:Effects of suramin, HPA-23 and 3'-azidothymidine triphosphate on the reverse transcriptase of bovine leukaemia virus. 246 27

We summarize the pathogenesis of animal lentiviruses (visna-maedi virus, caprine arthritis and encephalitis virus, and equine infectious anemia virus), which have raised considerable interest since the discovery of human lentiviruses. The human lentiviruses possess structural, genetic, and clinical properties similar to those of animal lentiviruses. We describe the different mechanisms of and the principal work on reverse transcriptase inhibitors of animal lentiviruses, such as HPA-23, phosphonoformate, or 2',3'-dideoxynucleosides. Animal viruses of this family may serve as models for infection with human lentiviruses such as human immunodeficiency virus, the etiologic agent of AIDS.
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PMID:Animal lentivirus replication and reverse transcriptase inhibitors. 247 76

HPA-23 is a competitive inhibitor of the RNA-dependent DNA polymerase (reverse transcriptase) of the human immunodeficiency virus (HIV). It may therefore potentially benefit patients with HIV infection. This study aimed at defining the haematopoietic toxicity of this drug and particularly its effects on the normal human granulocyte-macrophage progenitor cells (GM-CFU). Our in vitro studies, in semi-solid agar, have shown an inhibitory effect of increasing concentrations of HPA-23 on colony and cluster formation. This effect is probably dose-dependent. An almost complete inhibition of colony formation was observed at doses of more than 20 micrograms/ml. Regarding cluster formation, a similar although much more progressive inhibitory effect was found. Our experimental data should be extrapolated with caution to clinical situations. However, they must be kept in mind for optimal design of HPA-23 therapy in HIV infected patients.
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PMID:Toxicity of HPA-23 (ammonium-21-tungsto-9-antimoniate) for normal human myeloid progenitor cells (GM-CFU) in vitro. 259 Jul 21


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