title: Antiviral activity and possible mechanisms of action of pentagalloylglucose (PGG) against influenza A virus.
abstract: Influenza A virus (IAV) infection is a major public health threat leading to significant morbidity and mortality. The emergence of drug-resistant virus strains highlights the urgent need to develop novel antiviral drugs with alternative modes of action. Pentagalloylglucose (PGG), a naturally occurring polyphenolic compound, possesses a broad spectrum of biological activities. In this study, we found that PGG has anti-influenza-virus activity, and investigated its possible mechanism(s) of action in vitro. Both pre-incubation of virus prior to infection and post-exposure of infected cells with PGG significantly inhibited virus yields. Influenza-virus-induced hemagglutination of chicken red blood cells was inhibited by PGG treatment, suggesting that PGG can inhibit IAV infection by interacting with the viral hemagglutinin. PGG did not affect viral protein synthesis or nuclear transport of viral nucleoprotein (NP) but greatly reduced plasma membrane accumulation of NP protein at the late stage of the replication cycle. Furthermore, PGG significantly reduced virus budding and progeny virus release from infected cells. This study revealed for the first time that PGG can inhibit IAV replication with a dual mode of action and offers new insights into its underlying mechanisms of antiviral action.
authors.affiliation: Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki, Nagasaki, 852-8521, Japan.
authors.forename: Ge
authors.initials: G
authors.lastname: Liu
authors.forename: Sheng
authors.initials: S
authors.lastname: Xiong
authors.forename: Yang-Fei
authors.initials: YF
authors.lastname: Xiang
authors.forename: Chao-Wan
authors.initials: CW
authors.lastname: Guo
authors.forename: Feng
authors.initials: F
authors.lastname: Ge
authors.forename: Chong-Ren
authors.initials: CR
authors.lastname: Yang
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Wang
authors.forename: Kaio
authors.initials: K
authors.lastname: Kitazato
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002645:Chickens; D004285:Dogs; D004912:Erythrocytes; D006384:Hemagglutination / Q000187:drug effects; D006801:Humans; D047348:Hydrolyzable Tannins / Q000737:chemistry / Q000494:pharmacology*; D009980:Influenza A virus / Q000187:drug effects*; D029842:Phyllanthus emblica / Q000737:chemistry; D013237:Stereoisomerism; D053586:Virus Internalization / Q000187:drug effects; D057074:Virus Release / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D047348:Hydrolyzable Tannins; C435084:pentagalloylglucose