Bacitracin and the membrane-impermeant
thiol reagent 5,5'-dithiobis-2-nitrobenzoic
acid (
DTNB) are agents known to inhibit
protein disulfide isomerase (PDI), a
cell-surface protein critical in HIV-1 entry therefore they are fusion inhibitors (FI). Here we investigated the possibility that
Bacitracin and or
DTNB might have other
antiviral activities besides FI. By means of residual activity assays, we found that both compounds showed
antiviral activity only to viruses T-tropic HIV-1 strain. Cell-based fusion assays showed inhibition on HeLa-CD4-LTR-β-gal (CD4) and HL2/3 cells treated with
Bacitracin, and
DTNB with the latest compound we observed fusion inhibition on both cells but strikingly in HL2/3 cells (expressing Env) indicating a possible activity on both, the cell membrane and the viral envelope. A time-of-addition experiment showed that both compounds act on HIV entry inhibition but
DTNB also acts at late stages of the viral cycle. Lastly, we also found evidence of long-lasting host cell protection in vitro by
DTNB, an important pharmacodynamic parameter for a topical
microbicide against
virus infection, hours after the extracellular
drug was removed; this protection was not rendered by
Bacitracin. These drugs proved to be leading compounds for further studies against HIV showing
antiviral characteristics of interest.