Putative targeting by BX795 causes decrease in protein kinase C protein levels and inhibition of HSV1 infection.

Area of Science:

• Virology
• Molecular Biology
• Drug Discovery

Background:

• Herpes simplex virus type-1 (HSV1) utilizes host cellular machinery for replication.
• Current HSV1 treatments face challenges with toxicity and drug resistance.
• There is a need for novel antiviral agents with alternative mechanisms of action.

Purpose of the Study:

• To investigate the antiviral potential of the small molecule BX795 against HSV1.
• To elucidate the molecular mechanisms underlying BX795's antiviral activity.
• To explore the interaction of BX795 with host factors involved in HSV1 replication.

Main Methods:

• In silico analysis to predict interactions between BX795 and host factors.
• Treatment of HSV1-infected and mock-infected human corneal epithelial (HCE) cells with BX795.
• Assessment of protein levels and cellular localization of specific host factors (PKC isoforms).

Main Results:

• BX795 demonstrated in silico interaction with protein kinase C (PKC), a proviral host factor.
• BX795 significantly reduced the protein levels of PKC-α and PKC-ζ isoforms in HSV1-infected HCE cells.
• BX795 treatment decreased the perinuclear localization of PKC-α and PKC-ζ, similar to the known PKC inhibitor BIM I.

Conclusions:

• BX795 exhibits antiviral potential against HSV1 through a previously unrecognized mechanism.
• BX795 directly targets and modulates the activity of proviral PKC isoforms.
• This interaction with PKC represents a novel strategy for developing effective HSV1 therapies.