Schaftoside inhibits 3CL^(pro)and PL^(pro)of SARS-CoV-2 virus and regulates immune response and inflammation of host cells for the treatment of COVID-19

作     者：Yang Yi Meng Zhang Heng Xue Rong Yu Yang-Oujie Bao Yi Kuang Yue Chai Wen Ma Jing Wang Xiaomeng Shi Wenzhe Li Wei Hong Junhua Li Elishiba Muturi Hongping Wei Joachim Wlodarz Szczepan Roszak Xue Qiao Hang Yang Min Ye Yang Yi;Meng Zhang;Heng Xue;Rong Yu;Yang-Oujie Bao;Yi Kuang;Yue Chai;Wen Ma;Jing Wang;Xiaomeng Shi;Wenzhe Li;Wei Hong;Junhua Li;Elishiba Muturi;Hongping Wei;Joachim Wlodarz;Szczepan Roszak;Xue Qiao;Hang Yang;Min Ye

作者机构：State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China CAS Key Laboratory of Special Pathogens and BiosafetyCenter for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China University of Chinese Academy of SciencesBejing 100049China Faculty of Science and TechnologyUniversity of SilesiaKatowice 40-007Poland Department of Phrysical and Quantum ChenmistryFaculty of ChemistryWroclaw University of Science and Technology Wroclaw 50-370Poland 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2022年第12卷第11期

页      面：4154-4164页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by National Natural Science Foundation of China(Nos.81891010/81891011,81725023,82003614,82173950,31770192,32070187 and 82003681) China Postdoctoral Science Foundation(2022T150029,China) the National Key Research and Development Program of China(No.2017-YFC1700405) the Science&Technology Department of Xinjiang Uygur Autonomous Region(2018AB012,China) 

主　　题：COVID-19 SARS-CoV-2 3-Chymotrypsin-like protease Papain-like protease Licorice Schaftoside Immune response Infammation 

摘      要：It is an urgent demand worldwide to control the coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** 3-chymotrypsin-like protease(3CL^(pro))and papain-like protease(PL^(pro))are key targets to discover SARS-CoV-2 *** screening 12 Chinese herbal medicines and 125 compounds from licorice,we found that a popular natural product schaftoside inhibited 3CL^(pro)and PL^(pro)with IC_(50)values of 1.73±0.22 and 3.91±0.19μmol/L,respectively,and inhibited SARS CoV-2 virus in Vero E6 cells with EC_(50)of 11.83±3. 23μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The antiinflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.