In Vitro Anti-Orthohantavirus Activity of the High-and Low-Molecular-Weight Fractions of Fucoidan from the Brown Alga <i>Fucus evanescens</i>
Natalia V. Krylova,
Artem S. Silchenko,
Anastasia B. Pott,
Svetlana P. Ermakova,
Olga V. Iunikhina,
Anton B. Rasin,
Galina G. Kompanets,
Galina N. Likhatskaya,
Mikhail Y. Shchelkanov
Affiliations
Natalia V. Krylova
G.P. Somov Institute of Epidemiology and Microbiology, Rospotrebnadzor, Selskaya Street, 1, 690087 Vladivostok, Russia
Artem S. Silchenko
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 let Vladivostoku, 159, 690022 Vladivostok, Russia
Anastasia B. Pott
G.P. Somov Institute of Epidemiology and Microbiology, Rospotrebnadzor, Selskaya Street, 1, 690087 Vladivostok, Russia
Svetlana P. Ermakova
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 let Vladivostoku, 159, 690022 Vladivostok, Russia
Olga V. Iunikhina
G.P. Somov Institute of Epidemiology and Microbiology, Rospotrebnadzor, Selskaya Street, 1, 690087 Vladivostok, Russia
Anton B. Rasin
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 let Vladivostoku, 159, 690022 Vladivostok, Russia
Galina G. Kompanets
G.P. Somov Institute of Epidemiology and Microbiology, Rospotrebnadzor, Selskaya Street, 1, 690087 Vladivostok, Russia
Galina N. Likhatskaya
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 let Vladivostoku, 159, 690022 Vladivostok, Russia
Mikhail Y. Shchelkanov
G.P. Somov Institute of Epidemiology and Microbiology, Rospotrebnadzor, Selskaya Street, 1, 690087 Vladivostok, Russia
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.
