Antiherpetic Mechanism of a Sulfated Derivative of Agaricus brasiliensis Fruiting Bodies Polysaccharide

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 (CC 50 /EC 50 ) higher than 393. FR-S had no virucidal effect, but significantly suppressed HSV-1 (EC 50 = 0.32 µg/ml) and HSV-2 (EC 50 = 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 (EC 50 = 8.39 µg/ml) and HSV-2 (EC 50 = 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.