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

• Published in: Marine drugs Vol. 19; no. 10; p. 577
• Main Authors: Krylova, Natalia V, Silchenko, Artem S, Pott, Anastasia B, Ermakova, Svetlana P, Iunikhina, Olga V, Rasin, Anton B, Kompanets, Galina G, Likhatskaya, Galina N, Shchelkanov, Mikhail Y
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15-10-2021; MDPI
• Subjects: Algae; AMRV; Analytical methods; Animals; Antiviral activity; Antiviral agents; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Aquatic Organisms; Biological activity; Cell interactions; Drug development; Enzymes; fucanase GH107; Fucoidan; fucoidans; Fucus evanescens; Glycoproteins; Humans; Infections; Life cycle analysis; Microbial Sensitivity Tests; Molecular docking; Molecular Docking Simulation; Molecular Weight; NMR; NMR spectroscopy; Nuclear magnetic resonance; orthohantavirus; Orthohantavirus - drug effects; Phaeophyceae; Polysaccharides - chemistry; Polysaccharides - pharmacology; Spectroscopy; Spectrum analysis; Vero cells; Virus attachment; Viruses; fucanase GH107; orthohantavirus; molecular docking; antiviral activity; AMRV; fucoidans
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md19100577

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
(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 2
-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.