Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate a possible potentiation of Azidothymidine activity by immunomodulators, two in vitro models of HIV infection were analyzed. Peripheral blood lymphocytes on one hand, and cells from the CEM line on the other hand, were infected in vitro with HIV1 and reverse transcriptase activity was monitored daily in the cultures. When Azidothymidine was added, reverse transcriptase activity was significantly reduced. When Isoprinosine or Diethyldithiocarbamate was added in vitro, the reverse transcriptase was only slightly decreased (to a much less significant degree). When Azidothymidine was added together with either Isoprinosine or Diethyldithiocarbamate, a synergistic effect was observed with a very potent inhibition of reverse transcriptase activity. Before a possible application of such a combined therapy to patients, the pharmacokinetics of Azidothymidine was analyzed after the compound had been given alone or in combination with Isoprinosine. No alteration of pharmacokinetics was observed, suggesting that the immunomodulator will not alter the metabolism of the antiretroviral therapy in vivo, and may even enhance its biological activity, as it does in vitro.
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PMID:Rationale for a combined use of antiretroviral and immunomodulatory therapies in HIV infection. 172 84

Since clinical trials are being planned with the immunomodulating drug isoprinosine combined with the antiviral drug 3'-azido-3'-deoxythymidine (AZT) in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex, it is important to determine the type of antiviral interaction produced by these drugs in vitro. Such a combined modality may not only produce enhanced antiviral effects but also may have a valuable immunorestorative action. The interaction of several ratios of AZT and isoprinosine on the replication of human immunodeficiency virus type 1 in human peripheral blood mononuclear cells was determined by reverse transcriptase assay of disrupted virus obtained from supernatants of cells that were exposed to virus and the drugs separately and in combination and by a human immunodeficiency virus type 1 p24 enzyme immunoassay of the same supernatants. The correlation between the reverse transcriptase and enzyme immunoassay data was high. The antiviral activity of AZT alone was neither diminished nor augmented when AZT was used in combination with isoprinosine. Isoprinosine did not enhance virus yield when used alone or in combination with AZT in peripheral blood mononuclear cells, nor did it affect the growth of uninfected cells. The in vitro results indicate that this combination did not decrease the efficacy of AZT or exacerbate virus replication.
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PMID:Combinations of isoprinosine and 3'-azido-3'-deoxythymidine in lymphocytes infected with human immunodeficiency virus type 1. 246 87