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 (2021)
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
2021
1182
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202108256792
https://urn.fi/URN:NBN:fi:tuni-202108256792
Kuvaus
Peer reviewed
Tiivistelmä
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.
Kokoelmat
- TUNICRIS-julkaisut [16908]