Inhibition of the SARS-CoV-2 3CL$^{pro}$ main protease by plant polyphenols

Bahun, Miha (author), Jukič, Marko (author), Oblak, Domen (author), Kranjc, Luka (author), Bajc, Gregor (author), Butala, Matej (author), Bozovičar, Krištof (author), Bratkovič, Tomaž (author), Podlipnik, Črtomir (author), Poklar Ulrih, Nataša (author)

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 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.

• Language: English
• Keywords: edible plants, polyphenols, COVID-19, SARS-CoV-2, 3CL$^{pro}$, protease inhibitor
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty; FKKT - Faculty of Chemistry and Chemical Technology; FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 10 str.
• Numbering: Vol. 373, pt. B, art. 131594
• PID: 20.500.12556/RUL-134380
• UDC: 577.152.34:547.56
• ISSN on article: 0308-8146
• DOI: 10.1016/j.foodchem.2021.131594
• COBISS.SI-ID: 84899331
• Publication date in RUL: 12.01.2022

Record is a part of a journal

• Title: Food chemistry
• Shortened title: Food chem.
• Publisher: Elsevier
• ISSN: 0308-8146
• COBISS.SI-ID: 6385415

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: užitne rastline, fenolne spojine, inhibitorji proteaz, SARS-CoV-2 (virus)