Abstract
The efficacy of o,o'-bismyristoyl thiamine disulfide (BMT) was examined in detail against HIV-1 laboratory isolates (HTLV-IIIB, JRFL, and MN), primary isolates (KMT and KMO), and simian immunodeficiency virus (SIVmac251) in vitro. BMT inhibited the replication of HIV-1 in both laboratory and primary isolates in vitro. In addition, BMT exhibited antiviral activity against SIVmac251. Minimizing energy studies of BMT structure reveal that a trans-disulfide of thiamine (holo drug) disulfide (TDS, protodrug) is allosterically transited to the reactive twisted disulfide of BMT (allo drug) by o,o'-bismyristoyl esterification of TDS. BMT inhibits nuclear translocation of both HIV-1 transactivator (TAT) and the cellular transcriptional nuclear factor-KB (NF-kappa B), resulting in the suppression of HIV-1 replication.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Allosteric Site
-
Animals
-
Anti-HIV Agents / chemistry
-
Anti-HIV Agents / pharmacology*
-
COS Cells
-
Cell Line
-
Cell Nucleus / drug effects
-
Cell Nucleus / metabolism
-
Cell Nucleus / virology
-
Chlorocebus aethiops
-
Gene Products, tat / metabolism
-
HIV-1 / drug effects*
-
HIV-1 / isolation & purification
-
HIV-1 / physiology*
-
Humans
-
Leukocytes, Mononuclear / drug effects
-
Leukocytes, Mononuclear / metabolism
-
Leukocytes, Mononuclear / virology
-
Models, Molecular
-
Molecular Conformation
-
Molecular Structure
-
Myristates / chemistry
-
Myristates / pharmacology*
-
NF-kappa B / metabolism
-
Prodrugs / chemistry
-
Prodrugs / pharmacology
-
Simian Immunodeficiency Virus / drug effects
-
Simian Immunodeficiency Virus / physiology
-
Thiamine / chemistry
-
Thiamine / pharmacology*
-
Virus Replication / drug effects*
-
tat Gene Products, Human Immunodeficiency Virus
Substances
-
Anti-HIV Agents
-
Gene Products, tat
-
Myristates
-
NF-kappa B
-
O,O'-bismyristoyl thiamine disulfide
-
Prodrugs
-
tat Gene Products, Human Immunodeficiency Virus
-
Thiamine