Wogonin inhibits Varicella-Zoster (shingles) virus replication via modulation of type I interferon signaling and adenosine monophosphate-activated protein kinase activity

Abstract

Wogonin is a natural plant-derived flavonoid isolated from the roots of Scutellaria baicalensis. Varicella-zoster virus (VZV) is an α-herpesvirus, which causes chickenpox and shingles. Antiviral activities of natural plant-derived compounds against VZV have not been fully described. Here, we identify the significant inhibitory activity of wogonin against VZV replication. Transcription levels of the VZV genes such as open reading frame 4, 14, and 63 and infectious progeny virus were reduced with wogonin treatment in VZV-infected primary human fibroblast cells. Consistent to our polymerase chain reaction (PCR) array data, our qRT-PCR and ELISA data suggest wogonin treatment induced type I interferon (IFN)-mediated signaling pathways and activated toll-like receptor (TLR) 9 expression. Interestingly, wogonin specifically suppressed AMP-activated protein kinase (AMPK) activity and a pharmacological inhibition of AMPK by compound C resulted in the significant reduction of viral titers. Altogether, the data here indicate that wogonin has promising and potent anti-VZV activities.