title: Antiherpetic mechanism of a sulfated derivative of Agaricus brasiliensis fruiting bodies polysaccharide.
abstract: OBJECTIVE
  To study the anti-herpes simplex virus (HSV) activity of a (1→6)-(1→3)-β-D-glucan isolated from Agaricus brasiliensis fruiting bodies (FR) as well as its chemically sulfated derivative (FR-S).
  
  
  METHODS
  The antiherpetic activity and mechanism of action was studied by viral plaque assay applying different methodological strategies.
  
  
  RESULTS
  Although FR presented no in vitro antiherpetic action at 1 mg/ml, FR-S displayed promising anti-HSV-1 and anti-HSV-2 activities in both simultaneous and postinfection treatments, resulting in selectivity indices (CC₅₀/EC₅₀) higher than 393. FR-S had no virucidal effect, but significantly suppressed HSV-1 (EC₅₀ = 0.32 µg/ml) and HSV-2 (EC₅₀ = 0.10 µg/ml) adsorption. FR-S was less effective on adsorption inhibition of mutant virus strains devoid of gC (HSV-1 gC⁻39 and HSV-2 gCneg1), indicating a possible interaction with this glycoprotein. The reduction of viral adsorption upon cell pretreatment with FR-S also suggests its interaction with cellular components. FR-S inhibited HSV-1 (EC₅₀ = 8.39 µg/ml) and HSV-2 (EC₅₀ = 2.86 µg/ml) penetration more efficiently than heparin. FR-S reduced HSV-1 and HSV-2 cell-to-cell spread. A synergic effect between FR-S and acyclovir was also detected.
  
  
  CONCLUSIONS
  FR-S displays an interesting mechanism of antiviral action and represents a promising candidate for the treatment and/or prevention of herpetic infections, to be used as a single therapeutic agent or in combination with acyclovir.
authors.affiliation: Department of Infectious and Parasitic Diseases, Laboratory of Virology, Institute of Tropical Medicine, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Francielle Tramontini Gomes de Sousa
authors.initials: FT
authors.lastname: Cardozo
authors.forename: Carla Maísa
authors.initials: CM
authors.lastname: Camelini
authors.forename: Paulo César
authors.initials: PC
authors.lastname: Leal
authors.forename: Jadel Müller
authors.initials: JM
authors.lastname: Kratz
authors.forename: Ricardo José
authors.initials: RJ
authors.lastname: Nunes
authors.forename: Margarida Matos de
authors.initials: MM
authors.lastname: Mendonça
authors.forename: Cláudia Maria Oliveira
authors.initials: CM
authors.lastname: Simões
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D000364:Agaricus / Q000737:chemistry*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001938:Brazil; D002522:Chlorocebus aethiops; D004357:Drug Synergism; D048690:Fruiting Bodies, Fungal / Q000737:chemistry*; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D014709:Vero Cells; D010948:Viral Plaque Assay; D047071:beta-Glucans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D011134:Polysaccharides; D047071:beta-Glucans; D000212:Acyclovir