首页|Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation

Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation

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  • 国家科技期刊平台
  • NETL
  • NSTL
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Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

COVID-19InflammationLicorice-saponin A3Receptor-binding domain(RBD)SARS-CoV-2

Yang Yi、Wenzhe Li、Kefang Liu、Heng Xue、Rong Yu、Meng Zhang、Yang-Oujie Bao、Xinyuan Lai、Jingjing Fan、Yuxi Huang、Jing Wang、Xiaomeng Shi、Junhua Li、Hongping Wei、Kuanhui Xiang、Linjie Li、Rong Zhang、Xin Zhao、Xue Qiao、Hang Yang、Min Ye

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State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing,100191,China

CAS Key Laboratory of Pathogen Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing,100101,China

University of Chinese Academy of Sciences,Beijing,100049,China

Shenzhen Children's Hospital,Shenzhen,Guangdong,518036,China

CAS Key Laboratory of Special Pathogens and Biosafety,Center for Biosafety Mega-Science,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan,430071,China

Department of Microbiology and Infectious Disease Center,School of Basic Medical Sciences,Peking University Health Science Center,Peking University,Beijing,100191,China

Hubei Jiangxia Laboratory,Wuhan,430000,China

Yunnan Baiyao International Medical Research Center,Peking University,Beijing,100191,China

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国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金中国博士后科学基金

81891010/81891011817250238200361482173950317701923207018732161133003820036812022T150029

2024

10.1016/j.jpha.2023.05.011

药物分析学报(英文)
西安交通大学

药物分析学报(英文)

影响因子：0.244
ISSN：2095-1779
年,卷(期)：2024.14(1)
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