Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols.

[Display omitted] • Consensus docking is applied to evaluate binding of polyphenols to 3CLpro. • Ellagic acid is among strongest 3CLpro inhibitors of 19 polyphenols tested. • Ellagic acid binds into active site by hydrogen bonding and hydrophobic forces. • 3CLpro-polyphenols interactions are confirmed by surface plasmon resonance. The abundance of polyphenols in edible plants makes them an important component of human nutrition. Considering the ongoing COVID-19 pandemic, a number of studies have investigated polyphenols as bioactive constituents. We applied in-silico molecular docking as well as molecular dynamics supported by in-vitro assays to determine the inhibitory potential of various plant polyphenols against an important SARS-CoV-2 therapeutic target, the protease 3CLpro. Of the polyphenols in initial in-vitro screening, quercetin, ellagic acid, curcumin, epigallocatechin gallate and resveratrol showed IC 50 values of 11.8 µM to 23.4 µM. In-silico molecular dynamics simulations indicated stable interactions with the 3CLpro active site over 100 ns production runs. Moreover, surface plasmon resonance spectroscopy was used to measure the binding of polyphenols to 3CLpro in real time. Therefore, we provide evidence for inhibition of SARS-CoV-2 3CLpro by natural plant polyphenols, and suggest further research into the development of these novel 3CLpro inhibitors or biochemical probes. [ABSTRACT FROM AUTHOR]