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

Acta Pharmaceutica Sinica B (Dec 2022)

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

Affiliations

Dongrong Yi: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China
Quanjie Li: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China
Han Wang: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Kai Lv: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China
Ling Ma: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China
Yujia Wang: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China
Jing Wang: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China
Yongxin Zhang: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China
Mingliang Liu: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China
Xiaoyu Li: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China
Jianxun Qi: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Yi Shi: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authors.
George F. Gao: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
Shan Cen: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China; CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050, China; Corresponding authors.

Journal volume & issue: Vol. 12, no. 12
pp. 4378 – 4389

Abstract

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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.

Published in Acta Pharmaceutica Sinica B

ISSN: 2211-3835 (Print); 2211-3843 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/acta-pharmaceutica-sinica-b

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