title: Synergistic effects of acyclovir and 3, 19-isopropylideneandrographolide on herpes simplex virus wild types and drug-resistant strains.
abstract: BACKGROUND
  An andrographolide analogue, 3, 19-isopropylideneandrographolide (IPAD), exerts an inhibitory effect on replication of wild-type herpes simplex virus serotype 1 (HSV-1). In this study, we examined the anti-viral activity of IPAD on HSV wild types (HSV-1 strain KOS and HSV-2 clinical isolate) and HSV-1 drug-resistant strains (DRs). Synergistic effects of IPAD with acyclovir (ACV) were also evaluated.
  
  
  METHODS
  MTT and cytopathic effect (CPE) reduction assays were performed to determine cytotoxicity and anti-viral activities, respectively. A combination assay was used to determine synergistic effects of IPAD and ACV. Presence of viral DNA and protein in experimental cells was investigated using the polymerase chain reaction and western blotting, respectively.
  
  
  RESULTS
  A non-cytotoxic concentration of IPAD (20.50 μM) completely inhibited CPE formation induced by HSV wild types and HSV-1 DRs after viral entry into the cells. The anti-HSV activities included inhibition of viral DNA and protein synthesis. The minimum inhibitory concentrations of ACV for HSV wild types and HSV-1 DRs were 20.20 and 2,220.00 μM, respectively. Combination of ACV with IPAD showed synergistic effects in inhibition of CPE formation, viral DNA and protein synthesis by HSV wild types as well as HSV-1 DRs. For the synergistic effects on HSV wild types and HSV-1 DRs, the effective concentrations of ACV were reduced.
  
  
  CONCLUSIONS
  These results showed the inhibitory potential of IPAD on HSV wild types and HSV-1 DRs and suggested that IPAD could be used in combination with ACV for treatment of HSV-1 DRs infections.
authors: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. thong.koontoy2@hotmail.com.
authors: Thongkoon
authors: T
authors: Priengprom
authors: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. tipeka@kku.ac.th.|HPV & EBV and carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand. tipeka@kku.ac.th.
authors: Tipaya
authors: T
authors: Ekalaksananan
authors: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. bunkon@kku.ac.th.
authors: Bunkerd
authors: B
authors: Kongyingyoes
authors: Faculty of Pharmacy, Thammasat University, Bangkok, Thailand. hnungnet@yahoo.com.
authors: Supawadee
authors: S
authors: Suebsasana
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand. chaaro@kku.ac.th.|HPV & EBV and carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand. chaaro@kku.ac.th.
authors: Chantana
authors: C
authors: Aromdee
authors: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. chapie@kku.ac.th.|HPV & EBV and carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand. chapie@kku.ac.th.
authors: Chamsai
authors: C
authors: Pientong
mesh_terms: D000212:Acyclovir / Q000494:pharmacology*; D035685:Andrographis / Q000737:chemistry*; D000998:Antiviral Agents / Q000494:pharmacology; D004279:DNA, Viral; D004224:Diterpenes / Q000494:pharmacology*; D004351:Drug Resistance / Q000187:drug effects*; D004357:Drug Synergism; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010936:Plant Extracts / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D004224:Diterpenes; D010936:Plant Extracts; C030419:andrographolide; D000212:Acyclovir