ACTIVITY OF CU2ZN2 SUPEROXIDE-DISMUTASE AGAINST THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

The anti-retroviral activity of Cu2Zn2 superoxide dismutase (SOD; EC 1.15.1.1) was tested in Molt-4 cells infected with the human immunodeficiency virus type 1 (HIV-1) and compared to the anti-HIV-1 activity of the reverse transcriptase inhibitors azidothymidine (AZT), dideoxycytidine (ddC), dideoxyuridine (ddU) and phosphonoformic acid, the glucosidase I inhibitors castanospermine and dihydroxymethyl dihydroxy-pyrrolidine (DMDP), the HIV protease inhibitor RO-31-7595 as web as the CD4-masking compound aurintricarboxylic acid, 300 nM of SOD sufficed to reduce the release of the viral antigen gp 120 of HIV-1(NDK)-infected Molt-4 cells by 50% [EC(50)]. Cytotoxic effects of SOD were estimated by cell counts and rates of cell growth, SOD, 3 mu M, reduced the cell growth of uninfected cells by 50% [TC50]. While copper-free apo-SOD displayed no anti-HIV activity, the [EC(50)] of heat-inactivated enzyme was 1 mu M, suggesting an anti-retroviral effect of law molecular weight active center degradation products of SOD. The [EC(50)] of SOD reached 10% of AZT's anti-HTV-1(NDK) activity and exceeded all tested anti-retrovirals 40-3000-fold. The selectivity index (S-I=[TC50]/[EC(50)] for SOD was 10, resembling the reverse transcriptase inhibitors dideoxycytidine and phosphonoformic acid, SOD inhibited also dose-dependently the oxidative stress induced depletion of sulfhydryls, which are crucially involved in the nuclear factor kappa B controlled HIV transcription.