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Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication
Plant-based flavonoids have been evaluated as inhibitors of β-coronavirus replication and as therapies for COVID-19 on the basis of their safety profile and widespread availability. The SARS-CoV-2 main protease (Mpro) has been implicated as a target for flavonoids in silico. Yet no comprehensive in ...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470319/ https://www.ncbi.nlm.nih.gov/pubmed/37664626 http://dx.doi.org/10.1016/j.isci.2023.107602 |
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author | Lin, Lin Chen, Da-Yuan Scartelli, Christina Xie, Huanzhang Merrill-Skoloff, Glenn Yang, Moua Sun, Lijun Saeed, Mohsan Flaumenhaft, Robert |
author_facet | Lin, Lin Chen, Da-Yuan Scartelli, Christina Xie, Huanzhang Merrill-Skoloff, Glenn Yang, Moua Sun, Lijun Saeed, Mohsan Flaumenhaft, Robert |
author_sort | Lin, Lin |
collection | PubMed |
description | Plant-based flavonoids have been evaluated as inhibitors of β-coronavirus replication and as therapies for COVID-19 on the basis of their safety profile and widespread availability. The SARS-CoV-2 main protease (Mpro) has been implicated as a target for flavonoids in silico. Yet no comprehensive in vitro testing of flavonoid activity against SARS-CoV-2 Mpro has heretofore been performed. We screened 1,019 diverse flavonoids for their ability to inhibit SARS-CoV-2 Mpro. Multiple structure-activity relationships were identified among active compounds such as enrichment of galloylated flavonoids and biflavones, including multiple biflavone analogs of apigenin. In a cell-based SARS-CoV-2 replication assay, the most potent inhibitors were apigenin and the galloylated pinocembrin analog, pinocembrin 7-O-(3''-galloyl-4'',6''-(S)-hexahydroxydiphenoyl)-beta-D-glucose (PGHG). Molecular dynamic simulations predicted that PGHG occludes the S1 binding site via a galloyl group and induces a conformational change in Mpro. These studies will advance the development of plant-based flavonoids—including widely available natural products—to target β-coronaviruses. |
format | Online Article Text |
id | pubmed-10470319 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-104703192023-09-01 Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication Lin, Lin Chen, Da-Yuan Scartelli, Christina Xie, Huanzhang Merrill-Skoloff, Glenn Yang, Moua Sun, Lijun Saeed, Mohsan Flaumenhaft, Robert iScience Article Plant-based flavonoids have been evaluated as inhibitors of β-coronavirus replication and as therapies for COVID-19 on the basis of their safety profile and widespread availability. The SARS-CoV-2 main protease (Mpro) has been implicated as a target for flavonoids in silico. Yet no comprehensive in vitro testing of flavonoid activity against SARS-CoV-2 Mpro has heretofore been performed. We screened 1,019 diverse flavonoids for their ability to inhibit SARS-CoV-2 Mpro. Multiple structure-activity relationships were identified among active compounds such as enrichment of galloylated flavonoids and biflavones, including multiple biflavone analogs of apigenin. In a cell-based SARS-CoV-2 replication assay, the most potent inhibitors were apigenin and the galloylated pinocembrin analog, pinocembrin 7-O-(3''-galloyl-4'',6''-(S)-hexahydroxydiphenoyl)-beta-D-glucose (PGHG). Molecular dynamic simulations predicted that PGHG occludes the S1 binding site via a galloyl group and induces a conformational change in Mpro. These studies will advance the development of plant-based flavonoids—including widely available natural products—to target β-coronaviruses. Elsevier 2023-08-10 /pmc/articles/PMC10470319/ /pubmed/37664626 http://dx.doi.org/10.1016/j.isci.2023.107602 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Lin, Lin Chen, Da-Yuan Scartelli, Christina Xie, Huanzhang Merrill-Skoloff, Glenn Yang, Moua Sun, Lijun Saeed, Mohsan Flaumenhaft, Robert Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication |
title | Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication |
title_full | Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication |
title_fullStr | Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication |
title_full_unstemmed | Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication |
title_short | Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication |
title_sort | plant flavonoid inhibition of sars-cov-2 main protease and viral replication |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470319/ https://www.ncbi.nlm.nih.gov/pubmed/37664626 http://dx.doi.org/10.1016/j.isci.2023.107602 |
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