Antiherpetic activity of a sulfated polysaccharide from Agaricus brasiliensis mycelia

► Sulfation of Agaricus brasiliensis mycelial polysaccharide to obtain its sulfated derivative (MI-S). ► MI-S showed selectivity indices higher than 439, 208, and 562 for HSV-1 KOS, HSV-1 29R, and HSV-2 strain 333, respectively. ► MI-S presented multiple modes of anti-HSV action. ► MI-S inhibited HSV attachment, penetration, protein expression, and cell-to-cell spread. ► MI-S displayed synergistic antiviral effect with acyclovir.