Bioactive compounds of Jingfang Granules against SARS-CoV-2 virus proteases 3CLpro and PLpro
OBJECTIVE: Jingfang Granules have been recommended for the prevention and treatment of corona virus disease 2019 (COVID-19). Through chemical analysis and bioactivity evaluation, this study aims to elucidate the potential effective components of Jingfang Granules.
METHODS: The inhibitory acti-vities of Jingfang Granules extract against 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro), spike protein receptor-binding domain (S-RBD) and human cyclooxygenase-2 (COX-2) were evaluated using enzyme assay. The antitussive effects were evaluated using the classical ammonia-induced cough model. The chemical constituents of Jingfang Granules were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry (LC/MS). The 3CLpro and PLpro inhibitory activities of the major compounds were determined by enzyme assay, molecular docking, and site-directed mutagenesis.
RESULTS: Jingfang Granules exhibited 3CLpro and PLpro inhibitory activities, as well as COX-2 inhibitory and antitussive activities. By investigating the MS/MS behaviors of reference standards, a total of fifty-six compounds were characterized in Jingfang Granules. Sixteen of them were unambiguously identified by comparing with reference standards. The contents of the 16 major compounds were also determined, and their total contents were 2 498.8 μg/g. Naringin, nodakenin and neohesperidin were three dominating compounds in Jingfang Granules, and their contents were 688.8, 596.4 and 578.7 μg/g, respectively. In addition, neohesperidin and naringin exhibited PLpro inhibitory activities, and the inhibition rates at 8 μmol/L were 53.5% and 46.1%, respectively. Prim-O-glucosylcimifugin showed significant inhibitory activities against 3CLpro and PLpro, and the inhibitory rates at 8 μmol/L were 76.8% and 78.2%, respectively. Molecular docking indicated that hydrogen bonds could be formed between prim-O-glucosylcimifugin and amino acid residues H163, E166, Q192, T190 of 3CLpro (binding energy, -7.7 kcal/mol) and K157, D164, R166, E167, T301 of PLpro(-7.3 kcal/mol), respectively. Site-directed mutagenesis indicated amino acid residue K157 was a key active site for the interaction between prim-O-glucosylcimifugin and PLpro.
CONCLUSION: Prim-O-glucosylcimifugin, neohesperidin, and naringin as the major compounds from Jingfang Granules could inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus proteases 3CLpro and PLpro. The results are valuable for rational clinical use of Jingfang Granules.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:54 |
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| Enthalten in: |
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences - 54(2022), 5 vom: 18. Okt., Seite 907-919 |
| Sprache: |
Chinesisch |
|---|
| Beteiligte Personen: |
Shang, Z P [VerfasserIn] |
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| Anmerkungen: |
Date Completed 18.10.2022 Date Revised 02.11.2022 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM347562590 |
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| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a chi | ||
| 100 | 1 | |a Shang, Z P |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Bioactive compounds of Jingfang Granules against SARS-CoV-2 virus proteases 3CLpro and PLpro |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 18.10.2022 | ||
| 500 | |a Date Revised 02.11.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: Jingfang Granules have been recommended for the prevention and treatment of corona virus disease 2019 (COVID-19). Through chemical analysis and bioactivity evaluation, this study aims to elucidate the potential effective components of Jingfang Granules | ||
| 520 | |a METHODS: The inhibitory acti-vities of Jingfang Granules extract against 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro), spike protein receptor-binding domain (S-RBD) and human cyclooxygenase-2 (COX-2) were evaluated using enzyme assay. The antitussive effects were evaluated using the classical ammonia-induced cough model. The chemical constituents of Jingfang Granules were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry (LC/MS). The 3CLpro and PLpro inhibitory activities of the major compounds were determined by enzyme assay, molecular docking, and site-directed mutagenesis | ||
| 520 | |a RESULTS: Jingfang Granules exhibited 3CLpro and PLpro inhibitory activities, as well as COX-2 inhibitory and antitussive activities. By investigating the MS/MS behaviors of reference standards, a total of fifty-six compounds were characterized in Jingfang Granules. Sixteen of them were unambiguously identified by comparing with reference standards. The contents of the 16 major compounds were also determined, and their total contents were 2 498.8 μg/g. Naringin, nodakenin and neohesperidin were three dominating compounds in Jingfang Granules, and their contents were 688.8, 596.4 and 578.7 μg/g, respectively. In addition, neohesperidin and naringin exhibited PLpro inhibitory activities, and the inhibition rates at 8 μmol/L were 53.5% and 46.1%, respectively. Prim-O-glucosylcimifugin showed significant inhibitory activities against 3CLpro and PLpro, and the inhibitory rates at 8 μmol/L were 76.8% and 78.2%, respectively. Molecular docking indicated that hydrogen bonds could be formed between prim-O-glucosylcimifugin and amino acid residues H163, E166, Q192, T190 of 3CLpro (binding energy, -7.7 kcal/mol) and K157, D164, R166, E167, T301 of PLpro(-7.3 kcal/mol), respectively. Site-directed mutagenesis indicated amino acid residue K157 was a key active site for the interaction between prim-O-glucosylcimifugin and PLpro | ||
| 520 | |a CONCLUSION: Prim-O-glucosylcimifugin, neohesperidin, and naringin as the major compounds from Jingfang Granules could inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus proteases 3CLpro and PLpro. The results are valuable for rational clinical use of Jingfang Granules | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 3-chymotrypsin-like protease | |
| 650 | 4 | |a Effective components | |
| 650 | 4 | |a Jingfang Granules | |
| 650 | 4 | |a Papain like protease | |
| 650 | 4 | |a Severe acute respiratory syndrome coronavirus 2 | |
| 650 | 7 | |a Amino Acids |2 NLM | |
| 650 | 7 | |a Antitussive Agents |2 NLM | |
| 650 | 7 | |a Cyclooxygenase 2 Inhibitors |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 650 | 7 | |a Ammonia |2 NLM | |
| 650 | 7 | |a 7664-41-7 |2 NLM | |
| 650 | 7 | |a Cyclooxygenase 2 |2 NLM | |
| 650 | 7 | |a EC 1.14.99.1 |2 NLM | |
| 650 | 7 | |a Peptide Hydrolases |2 NLM | |
| 650 | 7 | |a EC 3.4.- |2 NLM | |
| 650 | 7 | |a Chymases |2 NLM | |
| 650 | 7 | |a EC 3.4.21.39 |2 NLM | |
| 650 | 7 | |a Cysteine Endopeptidases |2 NLM | |
| 650 | 7 | |a EC 3.4.22.- |2 NLM | |
| 650 | 7 | |a Papain |2 NLM | |
| 650 | 7 | |a EC 3.4.22.2 |2 NLM | |
| 650 | 7 | |a Coronavirus 3C Proteases |2 NLM | |
| 650 | 7 | |a EC 3.4.22.28 |2 NLM | |
| 700 | 1 | |a Yi, Y |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, R |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, J J |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Y X |e verfasserin |4 aut | |
| 700 | 1 | |a Qiao, X |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, M |e verfasserin |4 aut | |
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