title: Antiherpetic activity of a sulfated polysaccharide from Agaricus brasiliensis mycelia.
abstract: Sulfated polysaccharides are good candidates for drug discovery in the treatment of herpetic infections. Agaricus brasiliensis (syn A. subrufescens, A. blazei) is a Basidiomycete fungus native to the Atlantic forest region of Southeastern Brazil. Herein we report the chemical modification of a polysaccharide extracted from A. brasiliensis mycelia to obtain its sulfated derivative (MI-S), which presented a promising inhibitory activity against HSV-1 [KOS and 29R (acyclovir-resistant) strains] and HSV-2 strain 333, with selectivity indices (SI = CC50/IC50) higher than 439, 208, and 562, respectively. The mechanisms underlying this inhibitory activity were scrutinized by plaque assay with different methodological strategies. MI-S had no virucidal effects, but inhibited HSV-1 and HSV-2 attachment, penetration, and cell-to-cell spread, as well as reducing the expression of HSV-1 ICP27, UL42, gB, and gD proteins. MI-S also presented synergistic antiviral effect with acyclovir. These results suggest that MI-S presents multiple modes of anti-HSV action.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, 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: Alessandra
authors.initials: A
authors.lastname: Mascarello
authors.forename: Márcio José
authors.initials: MJ
authors.lastname: Rossi
authors.forename: Ricardo José
authors.initials: RJ
authors.lastname: Nunes
authors.forename: Célia Regina Monte
authors.initials: CR
authors.lastname: Barardi
authors.forename: Margarida Matos
authors.initials: MM
authors.lastname: de Mendonça
authors.forename: Cláudia Maria Oliveira
authors.initials: CM
authors.lastname: Simões
mesh_terms: D000364:Agaricus / Q000737:chemistry* / Q000254:growth & development; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D025282:Mycelium / Q000737:chemistry / Q000254:growth & development; D011134:Polysaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D011134:Polysaccharides