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 

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China [2]CAS Key Laboratory of Special Pathogens and Biosafety,Center for Biosafety Mega-Science,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan 430071,China [3]University of Chinese Academy of Sciences,Bejing 100049,China [4]Faculty of Science and Technology,University of Silesia,Katowice 40-007,Poland [5]Department of Phrysical and Quantum Chenmistry,Faculty of Chemistry,Wroclaw University of Science and Technology Wroclaw 50-370,Poland

出　　处：《Acta Pharmaceutica Sinica B》2022年第11期4154-4164,共11页药学学报（英文版）

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)。

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)virus.The 3-chymotrypsin-like protease(3CL^(pro))and papain-like protease(PL^(pro))are key targets to discover SARS-CoV-2 inhibitors.After 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.

关 键 词：COVID-19 SARS-CoV-2 3-Chymotrypsin-like protease Papain-like protease LICORICE Schaftoside Immune response Infammation 

分 类 号：R96[医药卫生—药理学]