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 com pounds tested, thiamine disulfide, alpha-lipoic acid, and N-acetylcyst eine significantly depressed HIV-1 Tat activity. Thiamine disulfide al one in these compounds possessing anti-HIV-Tat activity markedly inhib ited production of progeny HIV-1 in acute and chronic HIV-1-infected C EM at nontoxic concentrations of 500 similar to 1000 mu M. Thiamine di sulfide (500 mu M) blacked 99.7 % of HIV-1 production after 96 hr cult ure in acute HIV-1 (LAV-1) infection (m.o.i. = 0.002), whereas it inhi bited 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 thiamin e disulfide may be important for AIDS chemotherapy. (C) 1994 Academic Press, Inc.