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Efficient discovery of potential inhibitors for SARS-CoV-2 3C-like protease from herbal extracts using a native MS-based affinity-selection method

文献类型：期刊论文

作者Zhu, Dafu1,2,3; Su, Haixia3,4; Ke, Changqiang2; Tang, Chunping2; Witt, Matthias5; Quinn, Ronald J.6; Xu, Yechun3,4; Liu, Jia7,8; Ye, Yang1,2,3
刊名JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
出版日期2022-02-05
卷号209页码:8
关键词SARS-CoV-2 3CL protease Native MS Traditional Chinese medicine Natural product
ISSN号0731-7085
DOI10.1016/j.jpba.2021.114538
通讯作者Xu, Yechun(ycxu@simm.ac.cn) ; Liu, Jia(jia.liu@simm.ac.cn) ; Ye, Yang(yye@simm.ac.cn)
英文摘要The 3C-like protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential to the virus life cycle and is supposed to be a potential target for the treatment of coronaviral infection. Traditional Chinese medicines (TCMs) have played an impressive role in the treatment of COVID-19 in China. The effectiveness of TCM formulations prompts scientists to take continuous effort on searching for bioactive small molecules from the ancient resources. Herein, we developed a native mass spectrometry-based affinity-selection method for rapid screening of active small molecules from crude herbal extracts applied for COVID-19 therapy. Six common herbs named Lonicera japonica, Scutellaria baicalensis, Forsythia suspensa, Glycyrrhiza uralensis, Cirsium japonicum, and Andrographis paniculata were investigated. After preliminary separation of the crude extracts, the fractions were incubated with 3CLpro. A native MS-based affinity screening assay was then conducted to search for the protein-ligand complexes. A UHPLC-Q/TOF-MS with UNIFI data acquisition and data processing software was applied to identify the hit compounds. Standard compounds were used to verify the outcomes. Among the 16 hits, three flavonoids, baicalein, scutellarein and ganhuangenin, were identified as potential noncovalent inhibitors against 3CLpro with IC50 values of 1.14, 3.04, and 0.84 mu M, respectively. Their binding affinities were further characterized by native MS, with K-d values being 1.43, 3.85, and 1.09 mu M, respectively. Overall, we established an efficient native MS-based strategy for discovering 3CLpro ligands from crude mixtures, which supplies a potential strategy of small molecule lead discovery from TCMs. (C) 2021 Elsevier B.V. All rights reserved.
WOS关键词MASS-SPECTROMETRY
资助项目Science and Technology Commission of Shanghai Municipality[20430780300] ; National Natural Science Foundation of China[21920102003] ; Key-Area Research and Development Program of Guangdong Province[2020B0303070002]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000734880900007
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/300670]  
专题新药研究国家重点实验室
通讯作者Xu, Yechun; Liu, Jia; Ye, Yang
作者单位1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Nat Prod Chem Dept, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
5.Bruker Daltonik GmbH, D-28359 Bremen, Germany
6.Griffith Univ, Griffith Inst Drug Discovery, Brisbane, Qld 4111, Australia
7.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
8.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou 310058, Peoples R China
推荐引用方式
GB/T 7714		 Zhu, Dafu,Su, Haixia,Ke, Changqiang,et al. Efficient discovery of potential inhibitors for SARS-CoV-2 3C-like protease from herbal extracts using a native MS-based affinity-selection method[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2022,209:8.
APA Zhu, Dafu.,Su, Haixia.,Ke, Changqiang.,Tang, Chunping.,Witt, Matthias.,...&Ye, Yang.(2022).Efficient discovery of potential inhibitors for SARS-CoV-2 3C-like protease from herbal extracts using a native MS-based affinity-selection method.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,209,8.
MLA Zhu, Dafu,et al."Efficient discovery of potential inhibitors for SARS-CoV-2 3C-like protease from herbal extracts using a native MS-based affinity-selection method".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 209(2022):8.

入库方式： OAI收割

来源：上海药物研究所

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