Berberis lyceum and Fumaria indica : in vitro cytotoxicity, antioxidant activity, and in silico screening of their selected phytochemicals as novel hepatitis C virus nonstructural protein 5A inhibitors
Berberis lyceum and Fumaria indica are two Pakistani indigenous herbal medicines used to treat liver infections, including hepatitis C virus (HCV). This study aimed to evaluate the cytotoxicity, and antioxidant activity of these plant extracts and computationally screen their selected phytoconstituents as HCV NS5A inhibitors. The viability of HepG2 cells was assessed 24 h and 48 h post-treatment using colorimetric and dye exclusion methods. Antioxidant properties were examined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power, and total antioxidant capacity assays. Seventeen known phytochemicals identified from each plant were docked into the active binding site of HCV NS5A protein. The top hit ligands were analyzed for their druglikeness properties and the indices of absorption, distribution, metabolism, elimination, and toxicity (ADMET). The results showed that both plant extracts were non-toxic (CC50 > 200 µg/ml). The IC50 values of DPPH-radical scavenging activity were 51.02 ± 0.94 and 62.91 ± 1.85 µg/ml for B. lyceum and F. indica, respectively. They also exhibited reducing power and total antioxidant capacity.The phytochemicals were identified as potent HCV NS5A inhibitors with good druglikeness and ADMET properties. Six of the docked phytochemicals exhibited higher binding scores (-17.9 to -19.2 kcal/mol) with HCV NS5A protein than the standard drug, daclatasvir (-17.2 kcal/mol). Molecular dynamics (MD) simulation confirmed the stability of two compounds, berbamine and paprafumine at 100 ns with active site of HCV NS5A protein. The identified compounds through molecular docking and MD simulation could have potential as HCV NS5A inhibitor after further validation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
Journal of biomolecular structure & dynamics - 40(2022), 17 vom: 16. Okt., Seite 7829-7851 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Brice Landry, Koloko [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.09.2022 Date Revised 13.10.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/07391102.2021.1902395 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM323202659 |
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| 245 | 1 | 0 | |a Berberis lyceum and Fumaria indica |b in vitro cytotoxicity, antioxidant activity, and in silico screening of their selected phytochemicals as novel hepatitis C virus nonstructural protein 5A inhibitors |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Berberis lyceum and Fumaria indica are two Pakistani indigenous herbal medicines used to treat liver infections, including hepatitis C virus (HCV). This study aimed to evaluate the cytotoxicity, and antioxidant activity of these plant extracts and computationally screen their selected phytoconstituents as HCV NS5A inhibitors. The viability of HepG2 cells was assessed 24 h and 48 h post-treatment using colorimetric and dye exclusion methods. Antioxidant properties were examined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power, and total antioxidant capacity assays. Seventeen known phytochemicals identified from each plant were docked into the active binding site of HCV NS5A protein. The top hit ligands were analyzed for their druglikeness properties and the indices of absorption, distribution, metabolism, elimination, and toxicity (ADMET). The results showed that both plant extracts were non-toxic (CC50 > 200 µg/ml). The IC50 values of DPPH-radical scavenging activity were 51.02 ± 0.94 and 62.91 ± 1.85 µg/ml for B. lyceum and F. indica, respectively. They also exhibited reducing power and total antioxidant capacity.The phytochemicals were identified as potent HCV NS5A inhibitors with good druglikeness and ADMET properties. Six of the docked phytochemicals exhibited higher binding scores (-17.9 to -19.2 kcal/mol) with HCV NS5A protein than the standard drug, daclatasvir (-17.2 kcal/mol). Molecular dynamics (MD) simulation confirmed the stability of two compounds, berbamine and paprafumine at 100 ns with active site of HCV NS5A protein. The identified compounds through molecular docking and MD simulation could have potential as HCV NS5A inhibitor after further validation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Berberis lyceum | |
| 650 | 4 | |a Fumaria indica | |
| 650 | 4 | |a HCV NS5A | |
| 650 | 4 | |a antioxidant activity | |
| 650 | 4 | |a cytotoxicity | |
| 650 | 4 | |a in silico molecular docking | |
| 650 | 4 | |a molecular dynamics simulation | |
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| 650 | 7 | |a Antiviral Agents |2 NLM | |
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| 650 | 7 | |a Plant Extracts |2 NLM | |
| 650 | 7 | |a Viral Nonstructural Proteins |2 NLM | |
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| 700 | 1 | |a Malik, Ayesha |e verfasserin |4 aut | |
| 700 | 1 | |a Sufyan, Muhammad |e verfasserin |4 aut | |
| 700 | 1 | |a Ashfaq, Usman Ali |e verfasserin |4 aut | |
| 700 | 1 | |a Ijaz, Bushra |e verfasserin |4 aut | |
| 700 | 1 | |a Shahid, Ahmad Ali |e verfasserin |4 aut | |
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