In Vitro Anti-Orthohantavirus Activity of the High-and Low-Molecular-Weight Fractions of Fucoidan from the Brown Alga <i>Fucus evanescens</i>
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 fucoid...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/19/10/577 |
| _version_ | 1797514047096094720 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Natalia V. Krylova |
| collection | DOAJ |
| description | 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 <i>Fucus evanescens</i> (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<i>O</i>-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. |
| first_indexed | 2024-03-10T06:26:05Z |
| format | Article |
| id | doaj.art-8a29bd69d0df4416a83ff889488e931d |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T06:26:05Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-8a29bd69d0df4416a83ff889488e931d2023-11-22T18:55:40ZengMDPI AGMarine Drugs1660-33972021-10-01191057710.3390/md19100577In Vitro Anti-Orthohantavirus Activity of the High-and Low-Molecular-Weight Fractions of Fucoidan from the Brown Alga <i>Fucus evanescens</i>Natalia V. Krylova0Artem S. Silchenko1Anastasia B. Pott2Svetlana P. Ermakova3Olga V. Iunikhina4Anton B. Rasin5Galina G. Kompanets6Galina N. Likhatskaya7Mikhail Y. Shchelkanov8G.P. Somov Institute of Epidemiology and Microbiology, Rospotrebnadzor, Selskaya Street, 1, 690087 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 let Vladivostoku, 159, 690022 Vladivostok, RussiaG.P. Somov Institute of Epidemiology and Microbiology, Rospotrebnadzor, Selskaya Street, 1, 690087 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 let Vladivostoku, 159, 690022 Vladivostok, RussiaG.P. Somov Institute of Epidemiology and Microbiology, Rospotrebnadzor, Selskaya Street, 1, 690087 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 let Vladivostoku, 159, 690022 Vladivostok, RussiaG.P. Somov Institute of Epidemiology and Microbiology, Rospotrebnadzor, Selskaya Street, 1, 690087 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 let Vladivostoku, 159, 690022 Vladivostok, RussiaG.P. Somov Institute of Epidemiology and Microbiology, Rospotrebnadzor, Selskaya Street, 1, 690087 Vladivostok, RussiaThe 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 <i>Fucus evanescens</i> (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<i>O</i>-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.https://www.mdpi.com/1660-3397/19/10/577fucoidansfucanase GH107orthohantavirusAMRVantiviral activitymolecular docking |
| spellingShingle | 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 In Vitro Anti-Orthohantavirus Activity of the High-and Low-Molecular-Weight Fractions of Fucoidan from the Brown Alga <i>Fucus evanescens</i> Marine Drugs fucoidans fucanase GH107 orthohantavirus AMRV antiviral activity molecular docking |
| title | In Vitro Anti-Orthohantavirus Activity of the High-and Low-Molecular-Weight Fractions of Fucoidan from the Brown Alga <i>Fucus evanescens</i> |
| title_full | In Vitro Anti-Orthohantavirus Activity of the High-and Low-Molecular-Weight Fractions of Fucoidan from the Brown Alga <i>Fucus evanescens</i> |
| title_fullStr | In Vitro Anti-Orthohantavirus Activity of the High-and Low-Molecular-Weight Fractions of Fucoidan from the Brown Alga <i>Fucus evanescens</i> |
| title_full_unstemmed | In Vitro Anti-Orthohantavirus Activity of the High-and Low-Molecular-Weight Fractions of Fucoidan from the Brown Alga <i>Fucus evanescens</i> |
| title_short | In Vitro Anti-Orthohantavirus Activity of the High-and Low-Molecular-Weight Fractions of Fucoidan from the Brown Alga <i>Fucus evanescens</i> |
| title_sort | in vitro anti orthohantavirus activity of the high and low molecular weight fractions of fucoidan from the brown alga i fucus evanescens i |
| topic | fucoidans fucanase GH107 orthohantavirus AMRV antiviral activity molecular docking |
| url | https://www.mdpi.com/1660-3397/19/10/577 |
| work_keys_str_mv | AT nataliavkrylova invitroantiorthohantavirusactivityofthehighandlowmolecularweightfractionsoffucoidanfromthebrownalgaifucusevanescensi AT artemssilchenko invitroantiorthohantavirusactivityofthehighandlowmolecularweightfractionsoffucoidanfromthebrownalgaifucusevanescensi AT anastasiabpott invitroantiorthohantavirusactivityofthehighandlowmolecularweightfractionsoffucoidanfromthebrownalgaifucusevanescensi AT svetlanapermakova invitroantiorthohantavirusactivityofthehighandlowmolecularweightfractionsoffucoidanfromthebrownalgaifucusevanescensi AT olgaviunikhina invitroantiorthohantavirusactivityofthehighandlowmolecularweightfractionsoffucoidanfromthebrownalgaifucusevanescensi AT antonbrasin invitroantiorthohantavirusactivityofthehighandlowmolecularweightfractionsoffucoidanfromthebrownalgaifucusevanescensi AT galinagkompanets invitroantiorthohantavirusactivityofthehighandlowmolecularweightfractionsoffucoidanfromthebrownalgaifucusevanescensi AT galinanlikhatskaya invitroantiorthohantavirusactivityofthehighandlowmolecularweightfractionsoffucoidanfromthebrownalgaifucusevanescensi AT mikhailyshchelkanov invitroantiorthohantavirusactivityofthehighandlowmolecularweightfractionsoffucoidanfromthebrownalgaifucusevanescensi |