Repurposing of berbamine hydrochloride to inhibit Ebola virus by targeting viral glycoprotein |
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| Authors: | 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 |
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| Affiliation: | 1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China;2. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China;3. University of Chinese Academy of Sciences, Beijing 100049, China;4. CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050, China |
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| Abstract: | Ebola virus (EBOV) infection leads to staggeringly high mortality rate. Effective and low-cost treatments are urgently needed to control frequent EBOV outbreaks in Africa. In this study, we report that a natural compound called berbamine hydrochloride strongly inhibits EBOV replication in vitro and in vivo. Our 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 membranes. Our data support the probability of developing anti-EBOV small molecule drugs by targeting viral GPcl. More 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. |
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| Keywords: | Ebola virus Drug repositioning Entry inhibitor Primed glycoprotein Structure-based virtual screening Protein–protein interaction Berbamine hydrochloride Natural compound |
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