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Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

Pharmaceutics. 2021 Jul 31 ;13(8). Epub 2021 Jul 31. PMID: 34452144

Abstract Author(s):

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

Article Affiliation:

Dhanik Reshamwala

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 (10PFU/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.

Study Type : In Vitro Study

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