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 () and Kwok-Yung Yuen ()
Additional contact information
Shuofeng Yuan: The University of Hong Kong
Xin Yin: Chinese Academy of Agricultural Sciences
Xiangzhi Meng: The University of Hong Kong
Jasper Fuk-Woo Chan: The University of Hong Kong
Zi-Wei Ye: The University of Hong Kong
Laura Riva: Sanford Burnham Prebys Medical Discovery Institute
Lars Pache: Sanford Burnham Prebys Medical Discovery Institute
Chris Chun-Yiu Chan: The University of Hong Kong
Pok-Man Lai: The University of Hong Kong
Chris Chung-Sing Chan: The University of Hong Kong
Vincent Kwok-Man Poon: The University of Hong Kong
Andrew Chak-Yiu Lee: The University of Hong Kong
Naoko Matsunaga: Sanford Burnham Prebys Medical Discovery Institute
Yuan Pu: Sanford Burnham Prebys Medical Discovery Institute
Chun-Kit Yuen: The University of Hong Kong
Jianli Cao: The University of Hong Kong
Ronghui Liang: The University of Hong Kong
Kaiming Tang: The University of Hong Kong
Li Sheng: The University of Hong Kong
Yushen Du: University of California Los Angeles
Wan Xu: The University of Hong Kong
Chit-Ying Lau: The University of Hong Kong
Ko-Yung Sit: The University of Hong Kong, Queen Mary Hospital
Wing-Kuk Au: The University of Hong Kong, Queen Mary Hospital
Runming Wang: The University of Hong Kong
Yu-Yuan Zhang: Chinese Academy of Agricultural Sciences
Yan-Dong Tang: Chinese Academy of Agricultural Sciences
Thomas Mandel Clausen: University of California San Diego
Jessica Pihl: University of California San Diego
Juntaek Oh: University of California San Diego
Kong-Hung Sze: The University of Hong Kong
Anna Jinxia Zhang: The University of Hong Kong
Hin Chu: The University of Hong Kong
Kin-Hang Kok: The University of Hong Kong
Dong Wang: University of California San Diego
Xue-Hui Cai: Chinese Academy of Agricultural Sciences
Jeffrey D. Esko: University of California San Diego
Ivan Fan-Ngai Hung: The University of Hong Kong
Ronald Adolphus Li: The University of Hong Kong
Honglin Chen: The University of Hong Kong
Hongzhe Sun: The University of Hong Kong
Dong-Yan Jin: The University of Hong Kong
Ren Sun: The University of Hong Kong
Sumit K. Chanda: Sanford Burnham Prebys Medical Discovery Institute
Kwok-Yung Yuen: The University of Hong Kong

Nature, 2021, vol. 593, issue 7859, 418-423

Abstract: Abstract The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine—an anti-leprosy drug with a favourable safety profile3—possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and—when combined with remdesivir—in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and—possibly more importantly—in dealing with coronavirus diseases that may emerge in the future.

Date: 2021
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DOI: 10.1038/s41586-021-03431-4

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