A1 Journal article (refereed)
Polyphenols Epigallocatechin Gallate and Resveratrol, and Polyphenol-Functionalized Nanoparticles Prevent Enterovirus Infection through Clustering and Stabilization of the Viruses (2021)

Reshamwala, D., Shroff, S., Sheik, A. O., Laquintana, V., Denora, N., Zacheo, A., Lampinen, V., Hytonen, V. P., Tastan, B. Ö., Krol, S., & Marjomäki, V. (2021). Polyphenols Epigallocatechin Gallate and Resveratrol, and Polyphenol-Functionalized Nanoparticles Prevent Enterovirus Infection through Clustering and Stabilization of the Viruses. Pharmaceutics, 13(8), Article 1182. https://doi.org/10.3390/pharmaceutics13081182

JYU authors or editors

Publication details

All authors or editors: Reshamwala, Dhanik; Shroff, Sailee; Sheik, Amamuddy Olivier; Laquintana, Valentino; Denora, Nunzio; Zacheo, Antonella; Lampinen, Vili; Hytonen, Vesa P.; Tastan, Bishop Özlem; Krol, Silke; et al.

Journal or series: Pharmaceutics

eISSN: 1999-4923

Publication year: 2021

Publication date: 31/07/2021

Volume: 13

Issue number: 8

Article number: 1182

Publisher: MDPI AG

Publication country: Switzerland

Publication language: English

DOI: https://doi.org/10.3390/pharmaceutics13081182

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/77281

Abstract

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 (107 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.

Keywords: viruses; enteroviruses; infections; control (prevention); pharmacotherapy; nanoparticles; polyphenols; stabilisation (chemistry); epidemics; pandemics

Free keywords:  polyphenols; functionalized gold nanoparticles; antiviral efficacy; enteroviruses; stabilization

Contributing organizations

Ministry reporting: Yes

Reporting Year: 2021

JUFO rating: 1