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