Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols. (30th March 2022)

• Record Type: Journal Article
• Authors: Bahun, Miha; Jukić, Marko; Oblak, Domen; Kranjc, Luka; Bajc, Gregor; Butala, Matej; Bozovičar, Krištof; Bratkovič, Tomaž; Podlipnik, Črtomir; Poklar Ulrih, Nataša
• Is Part Of: Food chemistry. Volume 373:Part B(2022)
• Publication Date: 2022-03-30
• Subjects: caffeic acid (PubChem CID: 689043) -- chlorogenic acid (PubChem CID: 1794427) -- curcumin (PubChem CID: 969516) -- ellagic acid (PubChem CID: 5281855) -- epigallocatechin gallate (PubChem CID: 65064) -- ferulic acid (PubChem CID: 445858) -- galangin (PubChem CID: 5281616) -- 4-hydroxy-3-nitrophenylacetic acid (PubChem CID: 447364) -- isorhamnetin (PubChem CID: 5281654) -- kaempferol (PubChem CID: 5280863) -- kaempferol-rutinoside (PubChem CID: 5318767) -- phlorizin (PubChem CID: 6072) -- protocatechuic acid (PubChem CID: 72) -- quercetin (PubChem CID: 5280343) -- quinic acid (PubChem CID: 6508) -- resveratrol (PubChem CID: 445154) -- sinapic acid (PubChem CID: 637775) -- syringic acid (PubChem CID: 10742) -- umbellic acid (PubChem CID: 446611); Edible plants -- Polyphenols -- COVID-19 -- SARS-CoV-2 -- 3CLpro -- Protease inhibitor; Food -- Analysis -- Periodicals; Food -- Composition -- Periodicals; 664
• DOI: 10.1016/j.foodchem.2021.131594
• Languages: English
• ISSNs: 0308-8146

Abstract

Graphical abstract: Highlights: Consensus docking is applied to evaluate binding of polyphenols to 3CL pro . Ellagic acid is among strongest 3CL pro inhibitors of 19 polyphenols tested. Ellagic acid binds into active site by hydrogen bonding and hydrophobic forces. 3CL pro -polyphenols interactions are confirmed by surface plasmon resonance. Abstract: 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 IC50 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.