Polymethoxyflavone from Citrus depressa as an inhibitor against various variants of SARS-CoV-2 spike protein.
| Autor: | Liu TW; School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, 11042, Taiwan. Electronic address: d301110010@tmu.edu.tw., Hsu SJ; School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, 11042, Taiwan. Electronic address: juliashu1101@gmail.com., Hsieh YSY; School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, 11042, Taiwan; Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, 11042, Taiwan; Division of Glycoscience, Department of Chemistry, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, AlbaNova University Centre, Stockholm, SE106 91, Sweden. Electronic address: yvhsieh@kth.se., Liu HK; National Research Institute of Chinese Medicine (NRICM), Ministry of Health and Welfare, Taipei City, Taiwan; Ph. D. Program in the Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: hk.liu@nricm.edu.tw., Lee CK; School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, 11042, Taiwan; Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, 11042, Taiwan; Ph. D. Program in the Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: cklee@tmu.edu.tw. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of ethnopharmacology [J Ethnopharmacol] 2024 Feb 10; Vol. 320, pp. 117412. Date of Electronic Publication: 2023 Nov 21. |
| DOI: | 10.1016/j.jep.2023.117412 |
| Abstrakt: | Ethnopharmacological Relevance: In traditional Taiwanese medicine, Citrus depressa Hayata serves as the raw material of Chen-Pi which has been widely used to treat respiratory ailments. Scientific investigations have validated the attributes of C. depressa, elucidating its valuable properties, including antioxidative, anti-inflammatory, anticancer, neuroprotion, hepatoprotection, and hypolipidemic effects. Aim of the Study: This study aims to isolate a universal inhibitor of the SARS-CoV-2 spike protein from C. depressa and confirm the mechanism by which these inhibitors disrupt the binding of the spike protein to hACE2. Materials and Methods: The whole fruit of C. depressa was subjected to ethanol extraction, following by partitioning to obtain water, butanol, and ethyl acetate fractions. To identify the inhibitory components in citrus fruits, we performed both the SPR assay and the SARS-CoV-2 pseudo-virus assays. Subsequently, we employed a bioassay-guided approach to efficiently isolate and characterize the bioactive constituents that hindered the interaction between the SARS-CoV-2 spike protein and hACE2, using a combination of MPLC and Semi-preparative HPLC for compound isolation. ELISA based spike protein binding assay evaluate the inhibitory activities of the extract and potential constituents against multiple spike protein variants. To further shed light on the inhibitory mechanism, candidate inhibitors were validated through the SPR assay and molecular docking. Results: The crude extract and ethyl acetate layer derived from C. depressa showed significant inhibitory activity on SARS-CoV-2 Omicron BA.4/5, with IC Conclusion: This study presents the initial evidence showcasing the inhibitory effect of polymethoxyflavones (PMFs) on the spike protein of SARS-CoV-2. Moreover, the inhibitory activity of C. depressa extracts indicates their potential to prevent infections of different SARS-CoV-2 variants. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Databáze: | MEDLINE |
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