THIAMINE DISULFIDE AS A POTENT INHIBITOR OF HUMAN-IMMUNODEFICIENCY-VIRUS (TYPE-1) PRODUCTION

Thiol and disulfide compounds were tested as an anti-HIV drug against transactivator (Tat)-mediated transactivation of HIV-1. Of all the compounds tested, thiamine disulfide, alpha-lipoic acid, and N-acetylcysteine significantly depressed HIV-1 Tat activity. Thiamine disulfide alone in these compounds possessing anti-HIV-Tat activity markedly inhibited production of progeny HIV-1 in acute and chronic HIV-1-infected CEM at nontoxic concentrations of 500 similar to 1000 mu M. Thiamine disulfide (500 mu M) blacked 99.7 % of HIV-1 production after 96 hr culture in acute HIV-1 (LAV-1) infection (m.o.i. = 0.002), whereas it inhibited 90 similar to 98 % of HIV-1 production in chronic-infected cells (CEM/LAV-1, H9/MN, and Molt-4/IIIB). The results suggest that thiamine disulfide may be important for AIDS chemotherapy. (C) 1994 Academic Press, Inc.