Polyphenols epigallocatechin gallate and resveratrol, and polyphenol-functionalized nanoparticles prevent enterovirus infection through clustering and stabilization of the viruses

Dhanik Reshamwala, Sailee Shroff, Olivier Sheik Amamuddy, Valentino Laquintana, Nunzio Denora, Antonella Zacheo, Vili Lampinen, Vesa P. Hytonen, Özlem Tastan Bishop, Silke Krol, Varpu Marjomäki

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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.

Original languageEnglish
Article number1182
JournalPharmaceutics
Volume13
Issue number8
DOIs
Publication statusPublished - 2021
Publication typeA1 Journal article-refereed

Keywords

  • Antiviral efficacy
  • Enteroviruses
  • Functionalized gold nanoparticles
  • Polyphenols
  • Stabilization

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Pharmaceutical Science

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