title: Inhibition of herpes simplex virus infection by oligomeric stilbenoids through ROS generation.
abstract: Stilbenoids including resveratrol contain the basic structural unit of 1,2-diphenylethylene. Naturally occurring stilbenoids have broad structural features due to oligomerization and modifications and some have demonstrated potent biological activities. In an effort to identify bioactive stilbenoids, we screened a group of dimeric and oligomeric stilbenoids against HSV-1 and HSV-2 infection. Several trimeric and tetrameric derivatives showed anti-herpetic activity at single digit micromolar concentrations. HSV-1 and HSV-2 replication requires for NF-κB and MAPK activation. The compounds showed no inhibitory activity against NF-κB and Erk/MAPK activation, instead those compounds promoted rapid and transient release of reactive oxygen species (ROS). Addition of N-acetylcysteine (NAC), a scavenger of ROS, reversed the inhibitory effect of those compounds against HSV replication. In addition to the identification of resveratrol derivatives with potent anti-HSV activity, our results uncover a mechanism of polyphenol-mediated anti-HSV response, linking anti-herpetic activity of oligomeric stilbenoids to innate immunity.
authors.affiliation: Nanjing University School of Medicine and Jiangsu Laboratory of Molecular Medicine, Nanjing Jiangsu 210093, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Chen
authors.forename: Haishi
authors.initials: H
authors.lastname: Qiao
authors.forename: Taixiang
authors.initials: T
authors.lastname: Liu
authors.forename: Ziying
authors.initials: Z
authors.lastname: Yang
authors.forename: Lanfang
authors.initials: L
authors.lastname: Xu
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Xu
authors.forename: Hui Ming
authors.initials: HM
authors.lastname: Ge
authors.forename: Ren-Xiang
authors.initials: RX
authors.lastname: Tan
authors.forename: Erguang
authors.initials: E
authors.lastname: Li
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D016166:Free Radical Scavengers / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000111:Acetylcysteine