title: Proanthocyanidin-enriched extract from Myrothamnus flabellifolia Welw. exerts antiviral activity against herpes simplex virus type 1 by inhibition of viral adsorption and penetration.
abstract: OBJECTIVE
  Extracts from the aerial parts of the South African resurrection plant Myrothamnus flabellifolia Welw. have been used traditionally against infections of the upper respiratory tract and skin diseases. A polyphenol-enriched extract was investigated for potential antiviral effects against herpes simplex virus type 1 (HSV-1) and adenovirus, and the underlying mode of action was to be studied.
  
  
  METHODS
  Antiviral effects of an acetone-water extract (MF) from Myrothamnus flabellifolia on HSV-1 and adenovirus type 3 were tested in infected Vero cells by plaque reduction assay, MTT test and immunofluorescence. The influence of the extract on the HSV-1 envelope glycoprotein D was shown by Western blot. Organotypic full thickness skin models consisting of multilayer skin equivalents were used for the investigation of MF effects on HSV-1 replication.
  
  
  RESULTS
  MF exhibited strong antiviral activity against HSV-1. The HSV-1-specific inhibitory concentration (IC(50)) was determined as 0.4 μg/mL and the cytotoxic concentration (CC(50)) against Vero cells as 50 μg/mL. A selectivity index (SI) (ratio of CC(50) to IC(50)) of approximately 120 was calculated when MF was added to the virus inoculum for 1h at 37°C prior to infection. The replication of adenovirus 3 was not affected by MF. MF abolished virus entry into the host cell by blocking viral attachment to the cell surface. When added after attachment at a concentration of >6 μg/mL, the extract also inhibited penetration of HSV-1 into the host cell. Polyphenolic compounds from MF directly interacted with viral particles, leading to the oligomerisation of envelope proteins as demonstrated for the essential viral glycoprotein D (gD). Using organotypic full thickness tissue cultures, it was shown that treatment of HSV-1 infected cultures with the MF resulted in reduced viral spread.
  
  
  CONCLUSIONS
  A polyphenol-enriched extract from Myrothamnus flabellifolia strongly acts against HSV-1 by blocking viral entry into the cells.
authors.affiliation: Institute of Pharmaceutical Biology and Phytochemistry, University of Muenster, Hittorfstr. 56, D-48149 Muenster, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Gescher
authors.forename: Joachim
authors.initials: J
authors.lastname: Kühn
authors.forename: Eva
authors.initials: E
authors.lastname: Lorentzen
authors.forename: Wali
authors.initials: W
authors.lastname: Hafezi
authors.forename: Andrea
authors.initials: A
authors.lastname: Derksen
authors.forename: Alexandra
authors.initials: A
authors.lastname: Deters
authors.forename: Andreas
authors.initials: A
authors.lastname: Hensel
mesh_terms: D000256:Adenoviridae / Q000187:drug effects; D000257:Adenoviridae Infections / Q000382:microbiology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006561:Herpes Simplex / Q000188:drug therapy* / Q000382:microbiology; D018259:Herpesvirus 1, Human / Q000737:chemistry / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D020128:Inhibitory Concentration 50; D015603:Keratinocytes / Q000187:drug effects / Q000382:microbiology; D019684:Magnoliopsida / Q000737:chemistry*; D008517:Phytotherapy; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D044945:Proanthocyanidins / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects / Q000382:microbiology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry; D016662:Virus Integration / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D010936:Plant Extracts; D044945:Proanthocyanidins; D014759:Viral Envelope Proteins; C013221:proanthocyanidin