2. Academic Validation
  3. Clofazimine broadly inhibits coronaviruses including SARS-CoV-2

Clofazimine broadly inhibits coronaviruses including SARS-CoV-2

  • Nature. 2021 May;593(7859):418-423. doi: 10.1038/s41586-021-03431-4.
Shuofeng Yuan  # 1 2 3,  Xin Yin  # 4 5,  Xiangzhi Meng  # 2,  Jasper Fuk-Woo Chan  # 1 2 3 6,  Zi-Wei Ye  # 2,  Laura Riva 5 7,  Lars Pache 5,  Chris Chun-Yiu Chan 2,  Pok-Man Lai 2,  Chris Chung-Sing Chan 2,  Vincent Kwok-Man Poon 2,  Andrew Chak-Yiu Lee 2,  Naoko Matsunaga 5,  Yuan Pu 5,  Chun-Kit Yuen 2,  Jianli Cao 2,  Ronghui Liang 2,  Kaiming Tang 2,  Li Sheng 8 9,  Yushen Du 9,  Wan Xu 8,  Chit-Ying Lau 8,  Ko-Yung Sit 10,  Wing-Kuk Au 10,  Runming Wang 11,  Yu-Yuan Zhang 4,  Yan-Dong Tang 4,  Thomas Mandel Clausen 12 13,  Jessica Pihl 12 14,  Juntaek Oh 12 15,  Kong-Hung Sze 1 2,  Anna Jinxia Zhang 1 2,  Hin Chu 1 2,  Kin-Hang Kok 1 2,  Dong Wang 12 15,  Xue-Hui Cai 4,  Jeffrey D Esko 12 16,  Ivan Fan-Ngai Hung 17,  Ronald Adolphus Li 18,  Honglin Chen 1 2,  Hongzhe Sun 11,  Dong-Yan Jin 8,  Ren Sun 19 20,  Sumit K Chanda 21,  Kwok-Yung Yuen 22 23 24 25
Affiliations

Affiliations

  • 1 State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • 2 Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • 3 Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
  • 4 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
  • 5 Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
  • 6 Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University and The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • 7 Calibr, Scripps Research, La Jolla, CA, USA.
  • 8 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • 9 Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • 10 Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China.
  • 11 Department of Chemistry, State Key Laboratory of Synthetic Chemistry, CAS-HKU Joint Laboratory of Metallomics on Health and Environment, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • 12 Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
  • 13 Copenhagen Center for Glycomics, Department of Molecular and Cellular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • 14 Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • 15 Division of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
  • 16 Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA, USA.
  • 17 Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • 18 Dr Li Dak-Sum Research Centre, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • 19 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. rensun@hku.hk.
  • 20 Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. rensun@hku.hk.
  • 21 Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. schanda@sbpdiscovery.org.
  • 22 State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. kyyuen@hku.hk.
  • 23 Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. kyyuen@hku.hk.
  • 24 Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. kyyuen@hku.hk.
  • 25 Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University and The University of Hong Kong, Pokfulam, Hong Kong SAR, China. kyyuen@hku.hk.
  • # Contributed equally.
PMID: 33727703 DOI: 10.1038/s41586-021-03431-4
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.

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