Clofazimine: A Promising Inhibitor of Rabies Virus
Jiajing Wu, Shouchun Cao, Shan Lei, Qiang Liu, Yinghong Li, Yinghong Li, Yueyang Yu, Hui Xie, Qianqian Li, Xiao‐Qiang Zhao, Ruifeng Chen, Weijin Huang, Xinyue Xiao, Yongxin Yu, Danqing Song, Yuhua Li, Yuhua Li, Youchun Wang
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 EC 50 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.