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Discovery of naturally occurring inhibitors against SARS-CoV-2 3CLpro from Ginkgo biloba leaves via large-scale screening.

Authors
  • Xiong, Yuan1
  • Zhu, Guang-Hao2
  • Wang, Hao-Nan2
  • Hu, Qing2
  • Chen, Li-Li2
  • Guan, Xiao-Qing2
  • Li, Hui-Liang3
  • Chen, Hong-Zhuan2
  • Tang, Hui4
  • Ge, Guang-Bo5
  • 1 Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Pharmacy School of Shihezi University, Xinjiang, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China. , (China)
  • 2 Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China. , (China)
  • 3 School of Pharmacy, Second Military Medical University, Shanghai, China. , (China)
  • 4 Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Pharmacy School of Shihezi University, Xinjiang, China. Electronic address: [email protected] , (China)
  • 5 Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Fitoterapia
Publication Date
Jul 01, 2021
Volume
152
Pages
104909–104909
Identifiers
DOI: 10.1016/j.fitote.2021.104909
PMID: 33894315
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

3-Chymotrypsin-like protease (3CLpro) 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 3CLpro inhibitors from herbal constituents, as well as to investigate the inhibitory mechanism of the newly identified efficacious SARS-CoV-2 3CLpro inhibitors. Following screening of the inhibitory potentials of eighty herbal products against SARS-CoV-2 3CLpro, Ginkgo biloba leaves extract (GBLE) was found with the most potent SARS-CoV-2 3CLpro inhibition activity (IC50 = 6.68 μg/mL). Inhibition assays demonstrated that the ginkgolic acids (GAs) and the bioflavones isolated from GBLE displayed relatively strong SARS-CoV-2 3CLpro inhibition activities (IC50 < 10 μM). Among all tested constituents, GA C15:0, GA C17:1 and sciadopitysin displayed potent 3CLpro inhibition activities, with IC50 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 3CLprovia 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 3CLpro inhibition activities, which offer several promising leading compounds for developing novel anti-COVID-19 medications via targeting on 3CLpro. Copyright © 2021. Published by Elsevier B.V.

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