title: 3,19-isopropylideneandrographolide suppresses early gene expression of drug-resistant and wild type herpes simplex viruses.
abstract: A diterpenoid lactone, 3,19-isopropylideneandrographolide (IPAD) compound isolated from Andrographis paniculata (Burm. f.) Nees, has been reported to inhibit herpes simplex virus type 1 (HSV-1) infection at the post-entry step. To identify the molecular target of IPAD, this study characterized the inhibitory effect of IPAD on infection of Vero cells by HSV-1, HSV-2 and a drug-resistant (DR) HSV-1 strain ACGr4 (acyclovir-resistant and thymidine kinase (TK)-deficient). Viral production, gene and protein expression were determined using plaque assays, quantitative RT-PCR and western blotting, respectively. The results showed that IPAD inhibited HSV-1, HSV-2 and DR-HSV-1 infections at 6-12 h post-infection, a time that corresponded with E gene expression. IPAD completely suppressed ICP8 transcription and translation as well as DNA replication and gD expression in the three strains tested, while acyclovir suppressed transcription and translation of UL30 and gD of HSV-2, HSV-1, but had no effect on DR-HSV-1. These results showed that IPAD has a different molecular target from acyclovir and might therefore be an alternative drug for HSV-1 and HSV-2 wild types and DR-HSV-1 strains.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Bunkerd
authors.initials: B
authors.lastname: Kongyingyoes
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Thongkoon
authors.initials: T
authors.lastname: Priengprom
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Chamsai
authors.initials: C
authors.lastname: Pientong
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Chantana
authors.initials: C
authors.lastname: Aromdee
authors.affiliation: Faculty of Pharmacy, Thammasat University, Bangkok, Thailand.
authors.forename: Supawadee
authors.initials: S
authors.lastname: Suebsasana
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand. Electronic address: tipeka@kku.ac.th.
authors.forename: Tipaya
authors.initials: T
authors.lastname: Ekalaksananan
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D017781:Genes, Immediate-Early; D008826:Microbial Sensitivity Tests; D018139:Simplexvirus / Q000145:classification / Q000187:drug effects* / Q000502:physiology*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004224:Diterpenes; C030419:andrographolide
keywords: HSV-1; HSV-1 ACGr4; HSV-2; IPAD