Abstract

Oxidative stress is known to be a determinant of a host's susceptibility to pathogens. Natural compounds with antioxidant activity may provide a preventive measure against infection. Tea polyphenols were evaluated for their ability to inhibit enterovirus 71 (EV71) replication in Vero cell culture. Among the polyphenolic compounds tested, epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG) potently inhibited replication of EV71. EGCG and GCG reduced the titer of infectious progeny virus by 95%. Quantitative RT-PCR analysis also revealed that EGCG suppressed replication of genomic RNA. It was accompanied by an increased cytoprotective effect. EGCG and GCG caused 5-fold increase in the viability of EV71-infected cells. The viral inhibitory effect correlated well with the antioxidant capacity of polyphenol. Mechanistically, EV71 infection led to increased oxidative stress, as shown by increased dichlorofluorescein and MitoSOX Red fluorescence. Upon EGCG treatment, reactive oxygen species (ROS) generation was significantly reduced. Consistent with this, EV71 replication was enhanced in glucose-6-phosphate dehydrogenase deficient cells, and such enhancement was largely reversed by EGCG. These findings suggest that EGCG may suppress viral replication via modulation of cellular redox milieu.

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