Repurposing of berbamine hydrochloride to inhibit Ebola virus by targeting viral glycoprotein

作     者：Dongrong Yi Quanjie Li Han Wang Kai Lv Ling Ma Yujia Wang Jing Wang Yongxin Zhang Mingliang Liu Xiaoyu Li Jianxun Qi Yi Shi George F.Gao Shan Cen Dongrong Yi;Quanjie Li;Han Wang;Kai Lv;Ling Ma;Yujia Wang;Jing Wang;Yongxin Zhang;Mingliang Liu;Xiaoyu Li;Jianxun Qi;Yi Shi;George F.Gao;Shan Cen

作者机构：Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical SchoolBeijing 100050China CAS Key Laboratory of Pathogenic Microbiology and ImmunologyInstitute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of SciencesBeijing 100049China CAMS Key Laboratory of Antiviral Drug ResearchInstitute of Medicinal BiotechnologyPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100050China 

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

年 卷 期：2022年第12卷第12期

页      面：4378-4389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：This research was funded by the CAMS Innovation Fund for Medical Sciences(Grant Nos.2021-I2M-1-030 and CAMS-I2M-1-012,China) the National Natural Science Foundation of China(Grant Nos.81802019,81902075 and 81673358) the National Mega-project for Innovative Drugs(Grant No.2018ZX09711003-002-002,China) the Beijing Natural Science Foundation(Grant No.7184228,China) the Peking Union Medical College Youth Fund(Grant Nos.3332016063 and 3332018096,China) the China Ministry of Science and Technology National 973 Project(Grant No.2014CB542503) the Excellent Young Scientist Program from the NSFC(Grant No.81622031,China) the National Key Research and Development program of China(Grant No.2016YFD0500307) 

主　　题：Ebola virus Drug repositioning Entry inhibitor Primed glycoprotein Structure-based virtual screening Protein-protein interaction Berbamine hydrochloride Natural compound 

摘      要：Ebola virus(EBOV)infection leads to staggeringly high mortality *** and low-cost treatments are urgently needed to control frequent EBOV outbreaks in *** this study,we report that a natural compound called berbamine hydrochloride strongly inhibits EBOV replication in vitro and in *** work further showed that berbamine hydrochloride acts by directly binding to the cleaved EBOV glycoprotein(GPcl),disrupting GPcl interaction with viral receptor Niemann-Pick C1,thus blocking the fusion of viral and cellular *** data support the probability of developing anti-EBOV small molecule drugs by targeting viral *** importantly,since berbamine hydrochloride has been used in clinic to treat leukopenia,it holds great promise of being quickly repurposed as an anti-EBOV drug.