Lecithinized superoxide dismutase: an inhibitor of human immunodeficiency virus replication.
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.
Premanathan
M
M
Department of Microbiology and Immunology, Kagoshima University School of Dentistry, Japan.
Nakashima
H
H
Igarashi
R
R
Mizushima
Y
Y
Yamada
K
K
D019380:Anti-HIV Agents / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D015153:Blotting, Western; D002461:Cell Line, Transformed; D004347:Drug Interactions; D016333:HIV Protease / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010713:Phosphatidylcholines; D016133:Polymerase Chain Reaction; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D019380:Anti-HIV Agents; D010713:Phosphatidylcholines; D013482:Superoxide Dismutase; C072416:reverse transcriptase, Human immunodeficiency virus 2; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C065184:p16 protease, Human immunodeficiency virus 2