Antiviral activity of Schizonepeta tenuifolia Briquet against noroviruses via induction of antiviral interferons

Human noroviruses are the causative agents of non-bacterial gastroenteritis worldwide. The rapid onset and resolution of disease symptoms suggest that innate immune responses are critical for controlling norovirus infection; however, no effective antivirals are yet available. The present study was conducted to examine the antiviral activities of Schizonepeta tenuifolia Briquet extract (STE) against noroviruses. Treatment of human norovirus replicon-bearing HG23 cells with STE at 5 and 10 mg/ml concentrations resulted in the reduction in the viral RNA levels by 77.2% and 85.9%, respectively. STE had no cytotoxic effects on HG23 cells. Treatment of RAW 264.7 cells infected with murine norovirus 1 (MNV-1), a surrogate virus of human noroviruses, with STE at 10 and 20 µg/ml concentrations resulted in the reduction of viral replication by 58.5% and 84.9%, respectively. STE treatment induced the expression of mRNAs for type I and type II interferons in HG23 cells and upregulated the transcription of interferon-β in infected RAW 264.7 cells via increased phosphorylation of interferon regulatory factor 3, a critical transcription regulator for type I interferon production. These results suggest that STE inhibits norovirus replication through the induction of antiviral interferon production during virus replication and may serve as a candidate antiviral substance for treatment against noroviruses.