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)

Superoxide dismutase (SOD) is an enzyme used in the treatment of oxygen radical-related diseases. Lecithinization of SOD enhances its pharmacological activity. Lecithinized SOD (PC-SOD) inhibits human immunodeficiency virus (HIV) types 1 and 2 in MT-4 cells. HIV-1-infected MT-4 cells were cultured for 5 days in the presence of PC-SOD, at various concentrations. In an MTT assay, reverse transcriptase (RT) activity of the cell extract and p24 antigen production were measured. Untreated, HIV-1-infected MT-4 cells served as control. PC-SOD inhibited viral replication most effectively at 2500 U/ml, a concentration that did not affect cell viability, with an EC50 value of 718 U/ml. PC-SOD treatment inhibited RT activity and p24 production in a dose-dependent manner. Western blot analysis of the HIV-1-infected MT-4 cells treated with PC-SOD at 2500 U/ml did not detect any expression of viral proteins. Failure to inhibit virus adsorption, proviral DNA and mRNA synthesis, and RT and proteinase enzyme activity suggests that the mechanism of action of PC-SOD is entirely different from those of the currently available anti-HIV drugs. PC-SOD shows synergistic interaction with AZT, ddI, ddC, KNI-272, and dextran sulfate. PC-SOD also inhibited the oxidative stress-induced depletion of sulfhydryls, which are the cause of diminished antioxidant defenses in HIV-infected patients.
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PMID:Lecithinized superoxide dismutase: an inhibitor of human immunodeficiency virus replication. 907 27

We asked whether human immunodeficiency virus type 1 (HIV-1) protease plays a major role in the early stages of infection (i.e. from viral entry to reverse transcription) by using various protease inhibitors (saquinavir, ritonavir, and KNI-272). When assessed in the two-day multinuclear activation of a galactosidase indicator (MAGI) assay, involving a single cycle of HIV-1 replication, all protease inhibitors failed to block infection of HeLa-CD4-LTR-beta-gal cells by HIV-1, while reverse transcriptase (RT) inhibitors (AZT and ddI) completely blocked the infection. Moreover, when HIV-1 proviral DNA synthesis was examined by polymerase chain reaction in HeLa-CD4-LTR-beta-gal cells exposed to HIV-1 and cultured in the presence of protease inhibitors, a significant amount of proviral DNA was detected, while no proviral DNA synthesis was detected when the cells were cultured in the presence of RT inhibitors. Protease inhibitors also failed to block chloramphenicol acetyltransferase (CAT) expression in HLCD4-CAT cells exposed to HIV-1, while RT inhibitors completely suppressed CAT expression. These results strongly suggest, contrary to a previous report by Nagy et al. (1994), that HIV-1 protease does not play a major role in the early stages of infection.
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PMID:HIV-1 protease does not play a critical role in the early stages of HIV-1 infection. 944 67

Genetic recombination contributes to the genomic heterogeneity of human immunodeficiency virus type 1 (HIV-1). In the present study, we demonstrate that HIV-1 readily develops resistance to two classes of anti-HIV-1 drugs through in vitro genetic recombination involving large segments of the viral genome. Co-transfection of COS-7 cells with an HIV-1 plasmid (pSUM13) carrying five mutations in the reverse transcriptase (RT)-encoding region (A62V, V75I, F77L, F116Y, Q151M), conferring resistance to multiple dideoxynucleoside analogs (ddNs), and another HIV-1 plasmid (pSUM431) carrying five mutations in the protease-encoding region (V321, L33F, K451, 184V, L89M), conferring resistance to protease inhibitors such as KNI-272, readily produced HIV-1 carrying both sets of mutations when propagated in MT-2 cells in the presence of azidothymidine (AZT) and KNI-272. The resultant HIV-1 variant was highly resistant to both ddNs and KNI-272. Co-infection of MT-2 cells with HIV-1SUM13 carrying the RT mutations and HIV-1SUM431 carrying the mutations in the protease also generated HIV-1 with both sets of mutations when cultured with AZT and KNI-272. We also report here that the problematic artifactual recombination occurring during genetic analyses of heterogeneous nucleic acid sequences using polymerase chain reaction can be successfully obviated.
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PMID:HIV-1 acquires resistance to two classes of antiviral drugs through homologous recombination. 947 18