Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection

Yang Yi; Junhua Li; Xinyuan Lai; Meng Zhang; Yi Kuang; Yang-Oujie Bao; Rong Yu; Wei Hong; Elishiba Muturi; Heng Xue; Hongping Wei; Tong Li; Hui Zhuang; Xue Qiao; Kuanhui Xiang; Hang Yang; Min Ye

Journal of Advanced Research (Feb 2022)

Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection

Yang Yi,
Junhua Li,
Xinyuan Lai,
Meng Zhang,
Yi Kuang,
Yang-Oujie Bao,
Rong Yu,
Wei Hong,
Elishiba Muturi,
Heng Xue,
Hongping Wei,
Tong Li,
Hui Zhuang,
Xue Qiao,
Kuanhui Xiang,
Hang Yang,
Min Ye

Affiliations

Yang Yi: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China
Junhua Li: CAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China
Xinyuan Lai: Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, 38 Xueyuan Road, Beijing 100191, China
Meng Zhang: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China
Yi Kuang: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China
Yang-Oujie Bao: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China
Rong Yu: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China
Wei Hong: CAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China
Elishiba Muturi: CAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China
Heng Xue: CAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China
Hongping Wei: CAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China
Tong Li: Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, 38 Xueyuan Road, Beijing 100191, China
Hui Zhuang: Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, 38 Xueyuan Road, Beijing 100191, China
Xue Qiao: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China
Kuanhui Xiang: Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, 38 Xueyuan Road, Beijing 100191, China; Corresponding authors at: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China (M. Ye).
Hang Yang: CAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authors at: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China (M. Ye).
Min Ye: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China; Corresponding authors at: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China (M. Ye).

Journal volume & issue: Vol. 36
pp. 201 – 210

Abstract

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Introduction: The COVID-19 global epidemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a great public health emergency. Discovering antiviral drug candidates is urgent for the prevention and treatment of COVID-19. Objectives: This work aims to discover natural SARS-CoV-2 inhibitors from the traditional Chinese herbal medicine licorice. Methods: We screened 125 small molecules from Glycyrrhiza uralensis Fisch. (licorice, Gan-Cao) by virtual ligand screening targeting the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. Potential hit compounds were further evaluated by ELISA, SPR, luciferase assay, antiviral assay and pharmacokinetic study. Results: The triterpenoids licorice-saponin A3 (A3) and glycyrrhetinic acid (GA) could potently inhibit SARS-CoV-2 infection, with EC50 of 75 nM and 3.17 µM, respectively. Moreover, we reveal that A3 mainly targets the nsp7 protein, and GA binds to the spike protein RBD of SARS-CoV-2. Conclusion: In this work, we found GA and A3 from licorice potently inhibit SARS-CoV-2 infection by affecting entry and replication of the virus. Our findings indicate that these triterpenoids may contribute to the clinical efficacy of licorice for COVID-19 and could be promising candidates for antiviral drug development.

Published in Journal of Advanced Research

ISSN: 2090-1232 (Print); 2090-1224 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Science (General)
Website: http://www.journals.elsevier.com/journal-of-advanced-research/

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