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Polyphenols Epigallocatechin Gallate and Resveratrol, and Polyphenol-Functionalized Nanoparticles Prevent Enterovirus Infection through Clustering and Stabilization of the Viruses

To efficiently lower virus infectivity and combat virus epidemics or pandemics, it is important to discover broadly acting antivirals. Here, we investigated two naturally occurring polyphenols, Epigallocatechin gallate (EGCG) and Resveratrol (RES), and polyphenol-functionalized nanoparticles for the...

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Autores principales: Reshamwala, Dhanik, Shroff, Sailee, Sheik Amamuddy, Olivier, Laquintana, Valentino, Denora, Nunzio, Zacheo, Antonella, Lampinen, Vili, Hytonen, Vesa P., Tastan Bishop, Özlem, Krol, Silke, Marjomäki, Varpu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398301/
https://www.ncbi.nlm.nih.gov/pubmed/34452144
http://dx.doi.org/10.3390/pharmaceutics13081182
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author Reshamwala, Dhanik
Shroff, Sailee
Sheik Amamuddy, Olivier
Laquintana, Valentino
Denora, Nunzio
Zacheo, Antonella
Lampinen, Vili
Hytonen, Vesa P.
Tastan Bishop, Özlem
Krol, Silke
Marjomäki, Varpu
author_facet Reshamwala, Dhanik
Shroff, Sailee
Sheik Amamuddy, Olivier
Laquintana, Valentino
Denora, Nunzio
Zacheo, Antonella
Lampinen, Vili
Hytonen, Vesa P.
Tastan Bishop, Özlem
Krol, Silke
Marjomäki, Varpu
author_sort Reshamwala, Dhanik
collection PubMed
description To efficiently lower virus infectivity and combat virus epidemics or pandemics, it is important to discover broadly acting antivirals. Here, we investigated two naturally occurring polyphenols, Epigallocatechin gallate (EGCG) and Resveratrol (RES), and polyphenol-functionalized nanoparticles for their antiviral efficacy. Concentrations in the low micromolar range permanently inhibited the infectivity of high doses of enteroviruses (10(7) PFU/mL). Sucrose gradient separation of radiolabeled viruses, dynamic light scattering, transmission electron microscopic imaging and an in-house developed real-time fluorescence assay revealed that polyphenols prevented infection mainly through clustering of the virions into very stable assemblies. Clustering and stabilization were not compromised even in dilute virus solutions or after diluting the polyphenols-clustered virions by 50-fold. In addition, the polyphenols lowered virus binding on cells. In silico docking experiments of these molecules against 2- and 3-fold symmetry axes of the capsid, using an algorithm developed for this study, discovered five binding sites for polyphenols, out of which three were novel binding sites. Our results altogether suggest that polyphenols exert their antiviral effect through binding to multiple sites on the virion surface, leading to aggregation of the virions and preventing RNA release and reducing cell surface binding.
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spelling pubmed-83983012021-08-29 Polyphenols Epigallocatechin Gallate and Resveratrol, and Polyphenol-Functionalized Nanoparticles Prevent Enterovirus Infection through Clustering and Stabilization of the Viruses Reshamwala, Dhanik Shroff, Sailee Sheik Amamuddy, Olivier Laquintana, Valentino Denora, Nunzio Zacheo, Antonella Lampinen, Vili Hytonen, Vesa P. Tastan Bishop, Özlem Krol, Silke Marjomäki, Varpu Pharmaceutics Article To efficiently lower virus infectivity and combat virus epidemics or pandemics, it is important to discover broadly acting antivirals. Here, we investigated two naturally occurring polyphenols, Epigallocatechin gallate (EGCG) and Resveratrol (RES), and polyphenol-functionalized nanoparticles for their antiviral efficacy. Concentrations in the low micromolar range permanently inhibited the infectivity of high doses of enteroviruses (10(7) PFU/mL). Sucrose gradient separation of radiolabeled viruses, dynamic light scattering, transmission electron microscopic imaging and an in-house developed real-time fluorescence assay revealed that polyphenols prevented infection mainly through clustering of the virions into very stable assemblies. Clustering and stabilization were not compromised even in dilute virus solutions or after diluting the polyphenols-clustered virions by 50-fold. In addition, the polyphenols lowered virus binding on cells. In silico docking experiments of these molecules against 2- and 3-fold symmetry axes of the capsid, using an algorithm developed for this study, discovered five binding sites for polyphenols, out of which three were novel binding sites. Our results altogether suggest that polyphenols exert their antiviral effect through binding to multiple sites on the virion surface, leading to aggregation of the virions and preventing RNA release and reducing cell surface binding. MDPI 2021-07-31 /pmc/articles/PMC8398301/ /pubmed/34452144 http://dx.doi.org/10.3390/pharmaceutics13081182 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Reshamwala, Dhanik
Shroff, Sailee
Sheik Amamuddy, Olivier
Laquintana, Valentino
Denora, Nunzio
Zacheo, Antonella
Lampinen, Vili
Hytonen, Vesa P.
Tastan Bishop, Özlem
Krol, Silke
Marjomäki, Varpu
Polyphenols Epigallocatechin Gallate and Resveratrol, and Polyphenol-Functionalized Nanoparticles Prevent Enterovirus Infection through Clustering and Stabilization of the Viruses
title Polyphenols Epigallocatechin Gallate and Resveratrol, and Polyphenol-Functionalized Nanoparticles Prevent Enterovirus Infection through Clustering and Stabilization of the Viruses
title_full Polyphenols Epigallocatechin Gallate and Resveratrol, and Polyphenol-Functionalized Nanoparticles Prevent Enterovirus Infection through Clustering and Stabilization of the Viruses
title_fullStr Polyphenols Epigallocatechin Gallate and Resveratrol, and Polyphenol-Functionalized Nanoparticles Prevent Enterovirus Infection through Clustering and Stabilization of the Viruses
title_full_unstemmed Polyphenols Epigallocatechin Gallate and Resveratrol, and Polyphenol-Functionalized Nanoparticles Prevent Enterovirus Infection through Clustering and Stabilization of the Viruses
title_short Polyphenols Epigallocatechin Gallate and Resveratrol, and Polyphenol-Functionalized Nanoparticles Prevent Enterovirus Infection through Clustering and Stabilization of the Viruses
title_sort polyphenols epigallocatechin gallate and resveratrol, and polyphenol-functionalized nanoparticles prevent enterovirus infection through clustering and stabilization of the viruses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398301/
https://www.ncbi.nlm.nih.gov/pubmed/34452144
http://dx.doi.org/10.3390/pharmaceutics13081182
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