title: Pentagalloylglucose Blocks the Nuclear Transport and the Process of Nucleocapsid Egress to Inhibit HSV-1 Infection.
abstract: Herpes simplex virus type 1 (HSV-1), a widespread virus, causes a variety of human viral diseases worldwide. The serious threat of drug-resistance highlights the extreme urgency to develop 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 to be defined by further studies. 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. However, the over-expression of pEGFP-UL31 and pEGFP-UL34 could decrease the antiviral effect of PGG. In this study, for the first time, the antiviral activity of PGG against acyclovir-resistant virus was demonstrated in vitro, and the possible mechanisms of its anti-HSV activities were identified based on the inhibition of nuclear transport and nucleocapsid egress in HSV-1. It was further confirmed that PGG could be a promising candidate for HSV therapy, especially for drug-resistant strains.
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University.
authors.forename: Fujun
authors.initials: F
authors.lastname: Jin
authors.forename: Kaiqi
authors.initials: K
authors.lastname: Ma
authors.forename: Maoyun
authors.initials: M
authors.lastname: Chen
authors.forename: Muping
authors.initials: M
authors.lastname: Zou
authors.forename: Yanting
authors.initials: Y
authors.lastname: Wu
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Yifei
authors.initials: Y
authors.lastname: Wang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects*; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000378:metabolism*; D019251:Nucleocapsid / Q000187:drug effects*; D057074:Virus Release / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D047348:Hydrolyzable Tannins; C435084:pentagalloylglucose