Pentagalloylglucose blocks the nuclear transport and nucleocapsid egress process to inhibit HSV-1 infection

Abstract

Herpes simplex virus type 1 (HSV-1), a widespread virus, causes a variety of human viral diseases globally. The serious threat of drug-resistance highlights the extreme urgency of developing novel antiviral drugs with different mechanisms of action. Pentagalloylglucose (PGG) is a natural polyphenolic compound with significant anti-HSV activity; however, the mechanisms underlying its antiviral activity need further study to be defined. In this study, we found that PGG treatment delays the nuclear transport process of HSV-1 particles by inhibiting the upregulation of dynein (a cellular major motor protein) induced by HSV-1 infection. Furthermore, PGG treatment affects the nucleocapsid egress of HSV-1 by inhibiting the expression and disrupting the cellular localization of pEGFP-UL31 and pEGFP-UL34, which are indispensable for HSV-1 nucleocapsid egress from the nucleus. And the over-expression of pEGFP-UL31 and pEGFP-UL34 could weaken the antiviral activity of PGG. For the first time, PGG was demonstrated its antiviral activity against ACV-drug resistant virus in-vitro, and identified that the possible mechanisms of its anti-HSV activities were nuclear transport and nucleocapsid egress inhibition of HSV-1. It was confirmed that PGG could be a promising candidate for HSV therapy, especially for drug-resistant strains.