Antiviral anionic polysaccharides derived from a fungal beta-glucan

We chemically modified a β-glucan, botryosphaeran, to mimic the heparan sulfate (HS) present on the mammalian cellular surface as a receptor for non-enveloped viruses, such as dengue (DENV) and herpes (HSV) viruses. The derivatizations performed were: carboxymethylation/sulfation (CS), oxidation/sulfation (OS), nonspecific sulfation (NS) and regioselective sulfation (RS). Initially, CS and OS modifications were performed in order to transform the hydroxyl groups of the polysaccharide into carboxyl and sulfate groups. Despite their antiviral activity, potency was not satisfactory (higher IC50). Regarding NS, the insertion of only sulfate groups increased the antiviral activity, giving the lowest IC50 against HSV and DENV. For a more detailed SAR study, the synthesis of RS derivatives using protecting groups or mild sulfation conditions allowed regioselective sulfation of hydroxyl groups in positions 2 and 4, 2 or 6 of the glucose units. When the substitutions occurred in the OH-6 positions, better results for viral inhibition were obtained.