Chemically modified galactans of Grateloupia indica: From production to in vitro antiviral activity

Abstract

Herpes simplex viruses (HSVs) have an affinity for heparan sulfate proteoglycans on cell surfaces, which is adeterminant for virus entry. Herein, several sulfated galactans that mimic the active domain of the entry receptorwere employed to prevent HSV infection. They were produced from Grateloupia indica using chlorosulfonic acidpyridine(ClSO3H.Py)/N,N-dimethylformamide reagent (fraction G-402), SO3.Py/DMF reagent (G-403), or byaqueous extraction (G-401). These galactans contained varied molecular masses (33–55 kDa), and sulfate contents(12–20 %), and have different antiviral activities. Especially, the galactan (G-402) generated by usingClSO3H.Py/DMF, a novel reagent, exhibited the highest level of antiviral activity (EC50 = 0.36 μg/mL) comparedto G-403 (EC50 = 15.6 μg/mL) and G-401 (EC50 = 17.9 μg/mL). This most active sulfated galactan possessed alinear chain containing β-(1 → 3)- and α-(1 → 4)-linked Galp units with sulfate group at the O-2/4/6 and O-2/3/6positions, respectively. The HSV-1 and HSV-2 strains were specifically inhibited by this novel 33 ± 15 kDagalactan, which also blocked the virus from entering the host cell. These results highlight the significant potentialof this sulfated galactan for antiviral research and drug development. Additionally, the reagent used for theeffective conversion of galactan hydroxy groups to sulfate during extraction may also be useful for the chemicaltransformation of other natural products.