CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta,alpha,beta,and gamma

作     者：Jiejie Geng Liang Chen Yufeng Yuan Ke Wang Youchun Wang Chuan Qin Guizhen Wu Ruo Chen Zheng Zhang Ding Wei Peng Du Jun Zhang Peng Lin Kui Zhang Yongqiang Deng Ke Xu Jiangning Liu Xiuxuan Sun Ting Guo Xu Yang Jiao Wu Jianli Jiang Ling Li Kun Zhang Zhe Wang Jing Zhang Qingguo Yan Hua Zhu Zhaohui Zheng Jinlin Miao Xianghui Fu Fengfan Yang Xiaochun Chen Hao Tang Yang Zhang Ying Shi Yumeng Zhu Zhuo Pei Fei Huo Xue Liang Yatao Wang Qingyi Wang Wen Xie Yirong Li Mingyan Shi Huijie Bian Ping Zhu Zhi-Nan Chen Jiejie Geng;Liang Chen;Yufeng Yuan;Ke Wang;Youchun Wang;Chuan Qin;Guizhen Wu;Ruo Chen;Zheng Zhang;Ding Wei;Peng Du;Jun Zhang;Peng Lin;Kui Zhang;Yongqiang Deng;Ke Xu;Jiangning Liu;Xiuxuan Sun;Ting Guo;Xu Yang;Jiao Wu;Jianli Jiang;Ling Li;Kun Zhang;Zhe Wang;Jing Zhang;Qingguo Yan;Hua Zhu;Zhaohui Zheng;Jinlin Miao;Xianghui Fu;Fengfan Yang;Xiaochun Chen;Hao Tang;Yang Zhang;Ying Shi;Yumeng Zhu;Zhuo Pei;Fei Huo;Xue Liang;Yatao Wang;Qingyi Wang;Wen Xie;Yirong Li;Mingyan Shi;Huijie Bian;Ping Zhu;Zhi-Nan Chen

作者机构：National Translational Science Center for Molecular Medicine&Department of Cell BiologyFourth Military Medical UniversityXi'an 710032China School of MedicineShanghai UniversityShanghai 200444China Zhongnan Hospital of Wuhan UniversityWuhan 430071China Division of HIV/AIDS and Sex-transmitted Virus VaccinesInstitute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC)and WHO Collaborating Center for Standardization and Evaluation of BiologicalsBeijing 102629China Institute of Laboratory Animals ScienceChinese Academy of Medical SciencesBeijing 100071China NHC Key Laboratory of BiosafetyNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 100871China Beijing Institute of BiotechnologyBeijing 100871China Department of Clinical ImmunologyXijing HospitalFourth Military Medical UniversityXi'an 710032China Beijing Institute of Microbiology and EpidemiologyBeijing 100071China School of Basic MedicineFourth Military Medical UniversityXi'an 710032China Jiangsu Pacific Meinuoke Biopharmceutical Co.LtdChangzhou 213022China 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2021年第6卷第10期

页      面：3142-3154页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基　　金：supported by the National Science and Technology Major Project of China(2019ZX09732-001) the Key R&D Plan Projects in Shaanxi Province(2020ZDXM2-SF-01) the Young Talent Fund of the University Association for Science and Technology in Shaanxi,China(20200304) 

主　　题：CD147 cytokine storm 

摘      要：SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape,compromising the effectiveness of existing vaccines and neutralizing *** in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 ***,we identified CD147 as a universal receptor for SARS-CoV-2 and its ***,Meplazeumab,a humanized anti-CD147 antibody,could block cellular entry of SARS-CoV-2 and its variants-alpha,beta,gamma,and delta,with inhibition rates of 68.7,75.7,52.1,52.1,and 62.3%at 60μg/ml,***,humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants,alpha and *** infected,these mice developed exudative alveolar pneumonia,featured by immune responses involving alveoli-infiltrated macrophages,neutrophils,and lymphocytes and activation of IL-17 signaling ***,we proposed that severe COVID-19-related cytokine storm is induced by aspike protein-CD147-CyPA signaling axis:Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway,which further induced expression of cyclophilin A(CyPA);CyPA reciprocally bound to CD147 and triggered MAPK ***,the MAPK pathway regulated the expression of cytokines and chemokines,which promoted the development of cytokine ***,Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its ***,our findings provided a new perspective for severe COVID-19-related ***,the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.