Clofazimine: A Promising Inhibitor of Rabies Virus

Jiajing Wu; Shouchun Cao; Shan Lei; Qiang Liu; Yinghong Li; Yueyang Yu; Hui Xie; Qianqian Li; Xiaoqiang Zhao; Ruifeng Chen; Weijin Huang; Xinyue Xiao; Yongxin Yu; Danqing Song; Yuhua Li; Youchun Wang

doi:10.3389/fphar.2021.598241

Clofazimine: A Promising Inhibitor of Rabies Virus

Front Pharmacol. 2021 Mar 18:12:598241. doi: 10.3389/fphar.2021.598241. eCollection 2021.

Authors

Jiajing Wu^{1

2}, Shouchun Cao³, Shan Lei¹, Qiang Liu¹, Yinghong Li⁴, Yueyang Yu³, Hui Xie¹, Qianqian Li¹, Xiaoqiang Zhao⁴, Ruifeng Chen¹, Weijin Huang¹, Xinyue Xiao⁵, Yongxin Yu³, Danqing Song⁴, Yuhua Li³, Youchun Wang¹

Affiliations

¹ Department of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China.
² Wuhan Institute of Biological Products, Hubei, China.
³ Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China.
⁴ Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
⁵ Institute for Reference Standards and Standardization, National Institutes for Food and Drug Control, Beijing, China.

Abstract

With an almost 100% mortality rate, rabies virus (RABV) infection is a global concern. Limited post-exposure prophylaxis and lack of an effective treatment necessitate novel antiviral therapies against RABV. Here, using a high-throughput screening (HTS) method developed in our lab, 11 candidates with anti-RABV activity were identified from a library of 767 clinical drugs. Clofazimine (CFZ), an anti-leprosy drug, displayed an EC₅₀ of 2.28 μM, and SI over 967 against RABV. Investigations into the underlying mechanisms revealed that CFZ targeted viral membrane fusion at the early stages of virus replication. Moreover, CFZ and Clofazimine salicylates (CFZS) exhibited elevated survival rates in vivo, compared with the positive control T-705. Thus, this study revealed CFZ as a promising drug against RABV infection.

Keywords: approved drugs; clofazimine; high-throughput screening; in vivo; rabies virus.