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-acetycysteine 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 500-1000 microM. Thiamine disulfide (500 microM) blocked 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 90-98% 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.
Shoji
S
S
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Furuishi
K
K
Misumi
S
S
Miyazaki
T
T
Kino
M
M
Yamataka
K
K
D000111:Acetylcysteine / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015696:Gene Products, tat / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D013831:Thiamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008063:Thioctic Acid / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; D008063:Thioctic Acid; C013293:thiamine disulfide; D000111:Acetylcysteine; D013831:Thiamine