Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphonoformate, an inhibitor of reverse transcriptase in a number of retroviruses, was shown to have a dose-related inhibitory effect on human T-cell lymphotropic virus type III (HTLV-III) replication in the H9 cell line in vitro. HTLV-III replication was eliminated at a concentration of 680 mcgmol, a noncytotoxic dose. A lower dose of 132 mcgmol inhibited HTLV-III replication by more than 98%, as measured by reverse transcriptase activity, compared with untreated infected cultures. Reverse transcriptase activity in HTLV-III particles was completely inhibited by 5 mcgmol of phosphonoformate. Growth of uninfected H9 cells was not affected by the concentration of the drug. In clinical trials to treat cytomegalovirus infection in immunocompromised patients, constant serum levels of between 100-450 mcgmol of phosphonoformate have been achieved in 140 subjects. Further studies are recommended to evaluate the potential of phosphonoformate in patients infected with HTLV-III. It may be the least toxic of the antiviral agents that have been shown to have anti-HTLV-III activity.
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PMID:Inhibition of human T-cell lymphotropic virus type III in vitro by phosphonoformate. 240 14

The replicative cycle of the human immunodeficiency virus (HIV) is reviewed, and currently used and investigational agents directed against the virus are discussed. The first step in the replication of HIV is selective binding of the envelope glycoprotein to CD4 receptors located on T lymphocytes. The virion is then uncoated within the cytoplasm, yielding viral genomic RNA. Reverse transcriptase uses the viral RNA as a template to form single-stranded DNA, which is duplicated to form proviral DNA through the activity of ribonuclease H. Host RNA polymerases transcribe the integrated proviral DNA into messenger RNA, and there is subsequent translation to viral proteins. After translation, further modification of precursor polyproteins is necessary to produce functional peptides. The assembled virus then buds from the cell surface and invades other cells. Targets of drug intervention in the replicative cycle include (1) binding and entry, (2) reverse transcriptase, (3) transcription and translation, and (4) viral maturation and budding. Inhibitors of binding and entry include recombinant soluble CD4, immunoadhesins, peptide T, and hypericin. Nucleoside reverse-transcriptase inhibitors include zidovudine, didanosine, zalcitabine, and stavudine. Foscarnet, tetrahydroimidazobenzo-diazepinthione compounds, and nevirapine are some nonnucleoside reverse-transcriptase inhibitors. Inhibitors of transcription and translation include antagonists of the tat gene and GLQ223. Castanospermine, N-butyldeoxynojirimycin, and protease inhibitors interfere with viral maturation and budding. Drug combinations that have been or are being investigated include zidovudine plus interferon alfa, zidovudine plus zalcitabine, and zidovudine plus didanosine. Four agents currently have approved labeling for use against HIV infection: zidovudine, didanosine, zalcitabine, and stavudine. Monotherapy with zidovudine remains the treatment of first choice. Although progress has been made in developing drug therapies for HIV infection, more selective and more potent drugs are urgently needed. The best approach at present is to optimize the use of available agents, continue to investigate new therapies, and educate the public about prevention.
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PMID:Agents for treating human immunodeficiency virus infection. 775 75