Antiherpetic Mechanism of a Sulfated Derivative of <b><i>Agaricus brasiliensis</i></b> Fruiting Bodies Polysaccharide

Abstract

Objective: To study the anti-herpes simplex virus (HSV) activity of a (1→6)-(1→3)-β-<smlcap>D</smlcap>-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.

Fungal Cultivation and Production of Polysaccharides

“…Yamamoto et al (2013) found an anti-HSV-1 activity under simultaneous (EC 50 ¼ 454 mg/mL) and postinfection (83.6 % of inhibition at 800 mg/mL) treatments with PLS, using a viral plaque number reduction assay. Nonetheless, neither anti-HSV-1 nor anti-HSV-2 activity under these two treatments was found for FR at the maximum tested concentration (1 mg/ml) (Cardozo et al 2014).…”

“…FR-S had had no detectable protein content and lower molecular weight (127 kDa) in comparison to the non-sulfated version ). The introduction of sulfated groups on FR resulted in a sulfated derivative (FR-S) with promising in vitro antiherpetic activity (EC 50 < 6.74 mg/mL), acting by inhibition of HSV-1 and HSV-2 adsorption, penetration, and cell-tocell spread (Cardozo et al 2014). In a different way, SPLS did not demonstrate much improvement on antiviral activity after sulfation in the simultaneous treatment (EC 50 ¼ 346 mg/mL) and had no activity in the postinfection treatment (Yamamoto et al 2013).…”

Current Antivirals and Novel Botanical Molecules Interfering With Herpes Simplex Virus Infection

“…Sulfated compounds isolated from a polysaccharide (MI-S) derived from Agaricus brasiliensis have shown antiherpetic activity against HSV-1 and HSV-2 (De Sousa Cardozo et al, 2014). MI-S inhibited viral adsorption and penetration into Vero cells and had a synergistic effect with acyclovir (De Sousa Cardozo et al, 2014).…”

Efficacy of Pleuran (β‐Glucan from Pleurotus ostreatus) in the Management of Herpes Simplex Virus Type 1 Infection

“…Fungal and oat β-glucans exhibit in vitro antiherpetic activity and inhibit viral adsorption, penetration, and cellto-cell spread [11,25,26] and increase the macrophage proinflammatory cytokine response to HSV-1 infection [27]. erefore, they may represent potential prophylactic/ treatment agents in HSV-1 infection and can decrease susceptibility to viral infection following oral administration of β-glucans.…”