Prophylactic treatment with BX795 blocks activation of AKT and its downstream targets to protect vaginal keratinocytes and vaginal epithelium from HSV-2 infection

Genital herpes infections in humans are usually caused by herpes simplex virus type-2 (HSV-2), which result in recurrent lesions in the anogenital region. Past studies have shown that a viral protein translation inhibitor, BX795 is capable of mitigating HSV-2 infection both in vitro and in vivo when dosed therapeutically. However, any preventative benefits of this compound against HSV-2 infection remain poorly understood. In this study, we show that BX795 when added prophylactically to human vaginal keratinocytes generates strong preventative effects against a future HSV-2 infection. As a possible mechanism for this action, we found that BX795 efficiently reduces phosphorylation of AKT and its downstream targets p70S6K and 4EBP1. Our in-silico protein docking studies support our immunoblotting results and provide further credence to the proposed mechanism. Using a murine model of vaginal infection, we show that prior treatment with BX795 is also protective in vivo and leads to lower viral replication in the vaginal tissue.

Related Products

Cat.No. Product Name Information
S1274 BX-795 BX-795 is a potent and specific PDK1 inhibitor with IC50 of 6 nM, 140- and 1600-fold more selective for PDK1 than PKA and PKC in cell-free assays, respectively. Meanwhile, in comparison to GSK3β more than 100-fold selectivity observed for PDK1. BX-795 modulates autophagy via inhibiting ULK1. BX-795 also is a potent TBK1 inhibitor that blocks both TBK1 and IKKε with IC 50 values of 6 nM and 41 nM, respectively.

Related Targets

PDK Autophagy IκB/IKK