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Discovery of naturally occurring inhibitors against SARS-CoV-2 3CL(pro) from Ginkgo biloba leaves via large-scale screening

3-Chymotrypsin-like protease (3CL(pro)) is a virally encoded main proteinase that is pivotal for the viral replication across a broad spectrum of coronaviruses. This study aims to discover the naturally occurring SARS-CoV-2 3CL(pro) inhibitors from herbal constituents, as well as to investigate the...

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Autores principales: Xiong, Yuan, Zhu, Guang-Hao, Wang, Hao-Nan, Hu, Qing, Chen, Li-Li, Guan, Xiao-Qing, Li, Hui-Liang, Chen, Hong-Zhuan, Tang, Hui, Ge, Guang-Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Published by Elsevier B.V. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061081/
https://www.ncbi.nlm.nih.gov/pubmed/33894315
http://dx.doi.org/10.1016/j.fitote.2021.104909
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author Xiong, Yuan
Zhu, Guang-Hao
Wang, Hao-Nan
Hu, Qing
Chen, Li-Li
Guan, Xiao-Qing
Li, Hui-Liang
Chen, Hong-Zhuan
Tang, Hui
Ge, Guang-Bo
author_facet Xiong, Yuan
Zhu, Guang-Hao
Wang, Hao-Nan
Hu, Qing
Chen, Li-Li
Guan, Xiao-Qing
Li, Hui-Liang
Chen, Hong-Zhuan
Tang, Hui
Ge, Guang-Bo
author_sort Xiong, Yuan
collection PubMed
description 3-Chymotrypsin-like protease (3CL(pro)) is a virally encoded main proteinase that is pivotal for the viral replication across a broad spectrum of coronaviruses. This study aims to discover the naturally occurring SARS-CoV-2 3CL(pro) inhibitors from herbal constituents, as well as to investigate the inhibitory mechanism of the newly identified efficacious SARS-CoV-2 3CL(pro) inhibitors. Following screening of the inhibitory potentials of eighty herbal products against SARS-CoV-2 3CL(pro), Ginkgo biloba leaves extract (GBLE) was found with the most potent SARS-CoV-2 3CL(pro) inhibition activity (IC(50) = 6.68 μg/mL). Inhibition assays demonstrated that the ginkgolic acids (GAs) and the bioflavones isolated from GBLE displayed relatively strong SARS-CoV-2 3CL(pro) inhibition activities (IC(50) < 10 μM). Among all tested constituents, GA C15:0, GA C17:1 and sciadopitysin displayed potent 3CL(pro) inhibition activities, with IC(50) values of less than 2 μM. Further inhibition kinetic studies and docking simulations clearly demonstrated that two GAs and sciadopitysin strongly inhibit SARS-CoV-2 3CL(pro)via a reversible and mixed inhibition manner. Collectively, this study found that both GBLE and the major constituents in this herbal product exhibit strong SARS-CoV-2 3CL(pro) inhibition activities, which offer several promising leading compounds for developing novel anti-COVID-19 medications via targeting on 3CL(pro).
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spelling pubmed-80610812021-04-22 Discovery of naturally occurring inhibitors against SARS-CoV-2 3CL(pro) from Ginkgo biloba leaves via large-scale screening Xiong, Yuan Zhu, Guang-Hao Wang, Hao-Nan Hu, Qing Chen, Li-Li Guan, Xiao-Qing Li, Hui-Liang Chen, Hong-Zhuan Tang, Hui Ge, Guang-Bo Fitoterapia Article 3-Chymotrypsin-like protease (3CL(pro)) is a virally encoded main proteinase that is pivotal for the viral replication across a broad spectrum of coronaviruses. This study aims to discover the naturally occurring SARS-CoV-2 3CL(pro) inhibitors from herbal constituents, as well as to investigate the inhibitory mechanism of the newly identified efficacious SARS-CoV-2 3CL(pro) inhibitors. Following screening of the inhibitory potentials of eighty herbal products against SARS-CoV-2 3CL(pro), Ginkgo biloba leaves extract (GBLE) was found with the most potent SARS-CoV-2 3CL(pro) inhibition activity (IC(50) = 6.68 μg/mL). Inhibition assays demonstrated that the ginkgolic acids (GAs) and the bioflavones isolated from GBLE displayed relatively strong SARS-CoV-2 3CL(pro) inhibition activities (IC(50) < 10 μM). Among all tested constituents, GA C15:0, GA C17:1 and sciadopitysin displayed potent 3CL(pro) inhibition activities, with IC(50) values of less than 2 μM. Further inhibition kinetic studies and docking simulations clearly demonstrated that two GAs and sciadopitysin strongly inhibit SARS-CoV-2 3CL(pro)via a reversible and mixed inhibition manner. Collectively, this study found that both GBLE and the major constituents in this herbal product exhibit strong SARS-CoV-2 3CL(pro) inhibition activities, which offer several promising leading compounds for developing novel anti-COVID-19 medications via targeting on 3CL(pro). Published by Elsevier B.V. 2021-07 2021-04-22 /pmc/articles/PMC8061081/ /pubmed/33894315 http://dx.doi.org/10.1016/j.fitote.2021.104909 Text en © 2021 Published by Elsevier B.V. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Xiong, Yuan
Zhu, Guang-Hao
Wang, Hao-Nan
Hu, Qing
Chen, Li-Li
Guan, Xiao-Qing
Li, Hui-Liang
Chen, Hong-Zhuan
Tang, Hui
Ge, Guang-Bo
Discovery of naturally occurring inhibitors against SARS-CoV-2 3CL(pro) from Ginkgo biloba leaves via large-scale screening
title Discovery of naturally occurring inhibitors against SARS-CoV-2 3CL(pro) from Ginkgo biloba leaves via large-scale screening
title_full Discovery of naturally occurring inhibitors against SARS-CoV-2 3CL(pro) from Ginkgo biloba leaves via large-scale screening
title_fullStr Discovery of naturally occurring inhibitors against SARS-CoV-2 3CL(pro) from Ginkgo biloba leaves via large-scale screening
title_full_unstemmed Discovery of naturally occurring inhibitors against SARS-CoV-2 3CL(pro) from Ginkgo biloba leaves via large-scale screening
title_short Discovery of naturally occurring inhibitors against SARS-CoV-2 3CL(pro) from Ginkgo biloba leaves via large-scale screening
title_sort discovery of naturally occurring inhibitors against sars-cov-2 3cl(pro) from ginkgo biloba leaves via large-scale screening
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061081/
https://www.ncbi.nlm.nih.gov/pubmed/33894315
http://dx.doi.org/10.1016/j.fitote.2021.104909
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