In Vitro Anti-Orthohantavirus Activity of the High-and Low-Molecular-Weight Fractions of Fucoidan from the Brown Alga Fucus evanescens

The Hantaan orthohantavirus (genovariant Amur–AMRV) is a rodent-borne zoonotic virus; it is the causative agent of haemorrhagic fever with renal syndrome in humans. The currently limited therapeutic options require the development of effective anti-orthohantavirus drugs. The ability of native fucoidan from Fucus evanescens (FeF) and its enzymatically prepared high-molecular-weight (FeHMP) and low-molecular-weight (FeLMP) fractions to inhibit different stages of AMRV infection in Vero cells was studied. The structures of derivatives obtained were determined using nuclear magnetic resonance (NMR) spectroscopy. We found that fucoidan and its derivatives exhibited significant antiviral activity by affecting the early stages of the AMRV lifecycle, notably virus attachment and penetration. The FeHMP and FeLMP fractions showed the highest anti-adsorption activity by inhibiting AMRV focus formation, with a selective index (SI) > 110; FeF had an SI of ~70. The FeLMP fraction showed a greater virucidal effect compared with FeF and the FeHMP fraction. It was shown by molecular docking that 2O-sulphated fucotetrasaccharide, a main component of the FeLMP fraction, is able to bind with the AMRV envelope glycoproteins Gn/Gc and with integrin β3 to prevent virus–cell interactions. The relatively small size of these sites of interactions explains the higher anti-AMRV activity of the FeLMP fraction.

The Role of Sulfates in Fucoidan Extracted from Fucus evanescens in Proinflammatory Cytokines Production by Human Peripheral Blood Cells in vitro

Fucoidans, sulfated polysaccharides extracted from brown algae (Phaeophyceae), have a wide spectrum of bioactivity. Studies of molecular structures of fucoidans and deciphering of molecular elements' impact on their biological activities are at their active stage. The article shows the role of sulfates and acetyl groups in fucoidan isolated from Fucus evanescens in proinflammatory cytokines production by human heparinized unfractionated peripheral blood cells. Material and Methods. The cells were incubated with native fucoidan (N) and its deacetylated (deA), partially desulfated (deS), and both deacetylated and partially desulfated (deAdeS) derivatives (100 μg/mL). Cytokine concentrations were determined in cell supernatants by ELISA in a 'sandwich' modification with commercial kits. Results. Incubation with N fucoidan led to an increase of IL-6, TNF-α, IL-8 levels in supernatants. Partial removal of sulfate groups cancelled or decreased stimulating effect for IL-6, TNF-α, cytokines, but not for IL-8. deAc fucoidan action was comparable with N polysaccharide. Native polysaccharide and its chemically modified derivatives did not change IFN-γ и IL-10 cytokine production. Conclusion. The obtained results suggest that sulfates have a significant role in cytokine-producing properties of fucoidan extracted from brown algae F.evanescens.

Immunoadjuvant Activity of Fucoidans from the Brown Alga Fucus evanescens

The study presents the results of a comparative evaluation of the effect of structural modifications of fucoidans from the brown alga Fucus evanescens (native, highly purified product of fucoidan enzymatic hydrolysis, a new regular 1→3;1→4-α-L-fucan, sulphated mainly at C2 and acetylated at C4 of the fucose residue) on the effector functions of innate and adaptive immunity cells in vitro and in vivo. Using flow cytometry, we found that all examined fucoidans induce the maturation of dendritic cells, enhance the ability of neutrophils to migrate and adhere, activate monocytes and enhance their antigen-presenting functions, and increase the cytotoxic potential of natural killers. Fucoidans increase the production of hepatitis B virus (HBs) specific IgG and cytokine Th1 (IFN-γ, TNF-α) and Th2 (IL-4) profiles in vivo. The data obtained suggest that in vitro and in vivo adjuvant effects of the products of fucoidan enzymatic hydrolysis with regular structural characteristics are comparable to those of the native fucoidan. Based on these data, the products of fucoidan enzymatic hydrolysis can be considered as an effective and safe candidate adjuvant to improve the efficacy of prophylactic and therapeutic vaccines.