Clofazimine broadly inhibits coronaviruses including SARS-CoV-2

 Shuofeng Yuan, Xin Yin, Xiangzhi Meng, Jasper Fuk-Woo Chan, Zi-Wei Ye, Laura Riva, Lars Pache, Chris Chun-Yiu Chan, Pok-Man Lai, Chris Chung-Sing Chan, Vincent Kwok-Man Poon, Andrew Chak-Yiu Lee, Naoko Matsunaga, Yuan Pu, Chun-Kit Yuen, Jianli Cao, Ronghui Liang, Kaiming Tang, Li Sheng, Yushen Du, Wan Xu, Chit-Ying Lau, Ko-Yung Sit, Wing-Kuk Au, Runming Wang, Yu-Yuan Zhang, Yan-Dong Tang, Thomas Mandel Clausen, Jessica Pihl, Juntaek Oh, Kong-Hung Sze, Anna Jinxia Zhang, Hin Chu, Kin-Hang Kok, Dong Wang, Xue-Hui Cai, Jeffrey D. Esko, Ivan Fan-Ngai Hung, Ronald Adolphus Li, Honglin Chen, Hongzhe Sun, Dong-Yan Jin, Ren Sun, Sumit K. Chanda & Kwok-Yung Yuen

DOI:  https://doi.org/10.1038/ s41586-021-03431-4 (2021).

This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and fgures will undergo copyediting and a proof review before the paper is published in its fnal form. Please note that during the production process errors may be discovered which could afect the content, and all legal disclaimers apply.

COVID-19 pandemic is the third zoonotic coronavirus (CoV) outbreak of the century after severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) since 20122 . Treatment options for CoVs are largely lacking. Here we show that clofazimine, an anti-leprosy drug with a favourable safety profle3 , possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 and MERS-CoV replication in multiple in vitro systems. The FDA-approved molecule was found to inhibit viral spike-mediated cell fusion and viral helicase activity. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic or therapeutic administration of clofazimine signifcantly reduced viral load in the lung and faecal viral shedding, and also mitigated infammation associated with viral infection. Combinatorial application of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted upper respiratory tract viral shedding. Since clofazimine is orally bioavailable and has a comparatively low manufacturing cost, it is an attractive clinical candidate for outpatient treatment and remdesivir-based combinatorial therapy for hospitalized COVID-19 patients, particularly in developing countries. Taken together, our data provide evidence that clofazimine may have a role in the control of the current pandemic SARS-CoV-2, and, possibly most importantly, emerging CoVs of the future.

https://www.nature.com/articles/s41586-021-03431-4_reference.pdf