Study on the mechanism of active components of Liupao tea on 3CL ^pro based on HPLC‐DAD fingerprint and molecular docking technique

Abstract

Liupao tea, a drink homologous to medicine and food. It can treat dysentery, relieve heat, remove dampness, and regulate the intestines and stomach. The objective of this study is to explore the material basis and mechanism of Liupao tea intervention in COVID-19 and to provide a new prevention and treatment programme for COVID-19.We used high performance liquid chromatography to analyze the extract of Liupao tea and establish its fingerprint. The main index components of the fingerprint were determined using SARS-COV-2 3-chymotrypsin-like protease (3CL pro ), and an in vitro drug screening model based on fluorescence resonance energy transfer was used to evaluate its inhibitory activity in vitro. The fingerprint results showed that the alcohol extract of Liupao tea contained gallic acid, epigallocatechin gallate (EGCG), caffeine, epicatechin gallate, rutin, and ellagic acid. The molecular docking binding energies of the six index components of SARS-CoV-2 3Cl pro were all less than −5.0 kJ/mol and showed strong binding affinity. The results of in vitro activity showed that the IC 50 of EGCG was 8.84 μmol/L, which could inhibit SARS-CoV-2 3Cl pro to a certain extent. This study unleashed that EGCG has a certain inhibitory effect on SARS-CoV-2 3CL pro , and Liupao tea has a certain significance as a tea drink for the prevention of COVID-19. Practical applicationsThe objective of this study was to explore the material basis and mechanism of Liupao tea intervention in COVID-19 and to provide a new prevention and treatment programme for COVID-19. The molecular docking binding energies of the six index components of Liupao tea with SARS-CoV-2 3CL pro were all less than −5.0 kJ/mol, among them, the enzyme activity experiment shows that EGCG has a certain inhibitory effect on SARS-CoV-2 3CL pro , it can be used as a potential SARS-CoV-2 3CL pro How to cite this article: Ni W-J, Chen X-X, Wei S-Y, et al. Study on the mechanism of active components of Liupao tea on 3CL pro based on HPLC-DAD fingerprint and molecular docking technique.

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

“…An IC 50 for EGCG that was reported recently (0.056 µM) ( Du et al, 2021 ) was considerably lower than that in the present study (13.9 µM) ( Fig. 4 , and in other recent studies, at 4.2 µM ( Chiou et al, 2021 ) and 8.8 µM ( Ni et al, 2021 ). Interestingly, EGCG appears to inhibit SARS-CoV-2 3CL pro more strongly than SARS-CoV 3CL pro , which was demonstrated previously ( Chiou et al, 2021 ).…”

“…To the best of our knowledge, no previous studies have investigated the inhibition of SARS–CoV-2 by curcumin and resveratrol in-vitro . Ellagic acid is a tetracyclic polyphenol that is abundant in berries and nuts ( Daniel et al, 1989 ), and it was also previously predicted to inhibit SARS–CoV-2 3CL pro , although only in-silico ( Khalifa et al, 2020 , Ni et al, 2021 ). The present study confirms the strong inhibitory activity of ellagic acid against this protease in-vitro , with an IC 50 in the micromolar range.…”

“…The polyphenols that have shown in-vitro SARS-CoV-2 3CL pro inhibitory activity to date include epigallocatechin gallate (EGCG) ( Du et al, 2021 , Chiou et al, 2021 , Ni et al, 2021 ), quercetin ( Rizzuti et al, 2021 ), naringenin and kaempferol ( Du et al, 2021 ). In the present study, we screened several additional plant polyphenols for inhibition of SARS-CoV-2 3CL pro using a combination of in-vitro and in-silico approaches ( Fig.…”

Predicting global diet-disease relationships at the atomic level: a COVID-19 case study

“…For example, many highly-ranked compounds with predicted inhibitory activity against M pro contain polycyclic structures [ 22 • , 31 , 33 • ] or, in the case of peptides, amino acid residues containing ring structures [ 50 , 53 ]. Compounds such as epicatechin and its derivatives [ 23 , 27 , 44 • ] and hesperidin were also consistently ranked highly as candidate inhibitors of various targets involved in SARS-CoV-2 infection and replication [ 36 , 40 , 64 • , 65 • ]. Reviewing the results from multiple studies can provide additional context for the findings from standalone studies.…”

“…While examples of translatability between molecular docking results and clinical effect exist in drug discovery [ 15 ], such translations for food components and disease are less abundant. Epicatechin and its derivatives [ 27 , 44 • ] and high-ranking flavonoids [ 28 ] were reported to exhibit potent in vitro inhibitory activity against M pro . The antiviral activity of hesperidin against SARS-CoV-2 [ 65 • ] and hepatitis A virus as a model RNA virus has also been demonstrated in cellular and plaque assays, respectively [ 64 • ].…”