Yi Dongrong, Li Quanjie, Wang Han, Lv Kai, Ma Ling, Wang Yujia, Wang Jing, Zhang Yongxin, Liu Mingliang, Li Xiaoyu, Qi Jianxun, Shi Yi, Gao George F, Cen Shan
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Acta Pharm Sin B. 2022 Dec;12(12):4378-4389. doi: 10.1016/j.apsb.2022.05.023. Epub 2022 May 25.
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 and . 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.
埃博拉病毒（EBOV）感染导致极高的死亡率。迫切需要有效且低成本的治疗方法来控制非洲频繁爆发的埃博拉病毒疫情。在本研究中，我们报告了一种名为盐酸小檗胺的天然化合物能强烈抑制埃博拉病毒复制。我们的工作进一步表明，盐酸小檗胺通过直接结合裂解后的埃博拉病毒糖蛋白（GPcl）发挥作用，破坏GPcl与病毒受体尼曼-匹克C1的相互作用，从而阻断病毒膜与细胞膜的融合。我们的数据支持了通过靶向病毒GPcl开发抗埃博拉病毒小分子药物的可能性。更重要的是，由于盐酸小檗胺已在临床上用于治疗白细胞减少症，它极有希望被迅速重新用作抗埃博拉病毒药物。
