Inhibition of the SARS-CoV-2 3CL$^{pro}$ main protease by plant polyphenolsBahun, Miha (Avtor) Jukič, Marko (Avtor) Oblak, Domen (Avtor) Kranjc, Luka (Avtor) Bajc, Gregor (Avtor) Butala, Matej (Avtor) Bozovičar, Krištof (Avtor) Bratkovič, Tomaž (Avtor) Podlipnik, Črtomir (Avtor) Poklar Ulrih, Nataša (Avtor) edible plantspolyphenolsCOVID-19SARS-CoV-23CL$^{pro}$protease inhibitorThe 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 3CL $^{pro}$. 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 3CL $^{pro}$ active site over 100 ns production runs. Moreover, surface plasmon resonance spectroscopy was used to measure the binding of polyphenols to 3CL $^{pro}$ in real time. Therefore, we provide evidence for inhibition of SARS-CoV-2 3CL $^{pro}$ by natural plant polyphenols, and suggest further research into the development of these novel 3CL $^{pro}$ inhibitors or biochemical probes.20222022-01-12 10:54:59Članek v reviji134380sl