Clofazimine is a broad-spectrum coronavirus inhibitor that antagonizes SARS-CoV-2 replication in primary human cell culture and hamsters.
Shuofeng Yuan, Xin Yin, XiangZhi Meng, Jasper Chan, Zi-Wei Ye, Laura Riva, Lars Pache, Chris Chun-Yiu Chan, Pok-Man Lai, Chris Chan, Vincent Poon, Naoko Matsunaga, Yuan Pu, Chun-Kit Yuen, Jianli Cao, Ronghui Liang, Kaiming Tang, Li Sheng, Yushen Du, Wan Xu, Kong-Hung Sze, Jinxia Zhang, Hin Chu, Kin-Hang Kok, Kelvin To, Dong-Yan Jin, Ren Sun, Sumit Chanda, Kwok-Yung Yuen
Author Information
Shuofeng Yuan: University of Hong Kong.
Xin Yin: Sanford Burnham Prebys Medical Discovery Institute. ORCID
XiangZhi Meng: University of Hong Kong.
Jasper Chan: The University of Hong Kong.
Zi-Wei Ye: State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong.
Laura Riva: Sanford Burnham Prebys Medical Discovery Institute.
Lars Pache: Sanford Burnham Prebys Medical Discovery Institute. ORCID
Chris Chun-Yiu Chan: University of Hong Kong.
Pok-Man Lai: University of Hong Kong.
Chris Chan: The University of Hong Kong.
Vincent Poon: The University of Hong Kong.
Naoko Matsunaga: Sanford Burnham Prebys Medical Discovery Institute.
Yuan Pu: Sanford Burnham Prebys Medical Discovery Institute.
Chun-Kit Yuen: University of Hong Kong.
Jianli Cao: The University of Hong Kong.
Ronghui Liang: University of Hong Kong.
Kaiming Tang: University of Hong Kong.
Li Sheng: UCLA.
Yushen Du: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA. ORCID
COVID-19 pandemic is the third zoonotic coronavirus (CoV) outbreak of the century after severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) since 2012. Treatment options for CoVs are largely lacking. Here, we show that clofazimine, an anti-leprosy drug with a favorable safety and pharmacokinetics profile, possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 replication in multiple systems, including the human embryonic stem cell-derived cardiomyocytes and lung cultures. The FDA-approved molecule was found to inhibit multiple steps of viral replication, suggesting multiple underlying antiviral mechanisms. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic or therapeutic administration of clofazimine significantly reduced viral load in the lung and fecal viral shedding, and also prevented cytokine storm associated with viral infection. Additionally, clofazimine exhibited synergy when administered with remdesivir. 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, endemic MERS-CoV in the Middle East, and, possibly most importantly, emerging CoVs of the future.
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