Abstract
The efficacy ofo,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 isolatesin 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) byo, o′-bismyristoyl esterification of TDS. BMT inhibits nuclear translocation of both HIV-1 transactivator (Tat) and the cellular transcriptional nuclear factor-κB (NF-κB), resulting in the suppression of HIV-1 replication.
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