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The hyperlipidaemic drug fenofibrate significantly reduces infection by SARS-CoV-2 in cell culture models

View ORCID ProfileScott P. Davies, Courtney J. Mycroft-West, View ORCID ProfileIsabel Pagani, View ORCID ProfileHarriet J. Hill, View ORCID ProfileYen-Hsi Chen, View ORCID ProfileRichard Karlsson, View ORCID ProfileIeva Bagdonaite, View ORCID ProfileScott E. Guimond, View ORCID ProfileZania Stamataki, Marcelo Andrade De Lima, View ORCID ProfileJeremy E. Turnbull, Zhang Yang, View ORCID ProfileElisa Vicenzi, View ORCID ProfileMark A. Skidmore, View ORCID ProfileFarhat Khanim, View ORCID ProfileAlan Richardson
doi: https://doi.org/10.1101/2021.01.10.426114
Scott P. Davies
1Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, United Kingdom
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Courtney J. Mycroft-West
2Molecular & Structural Bioscience, School of Life Sciences, Keele University, Staffordshire, ST5 5BG, United Kingdom
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Isabel Pagani
3Viral Pathogenesis and Biosafety Unit, San Raffaele Scientific Institute, Via Olgettina, 58, Milano, Italy
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  • ORCID record for Isabel Pagani
Harriet J. Hill
1Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, United Kingdom
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Yen-Hsi Chen
4Copenhagen Center for Glycomics, Department of Cellular & Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen N 2200, Denmark
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Richard Karlsson
4Copenhagen Center for Glycomics, Department of Cellular & Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen N 2200, Denmark
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Ieva Bagdonaite
4Copenhagen Center for Glycomics, Department of Cellular & Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen N 2200, Denmark
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Scott E. Guimond
2Molecular & Structural Bioscience, School of Life Sciences, Keele University, Staffordshire, ST5 5BG, United Kingdom
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  • ORCID record for Scott E. Guimond
Zania Stamataki
1Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, United Kingdom
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  • ORCID record for Zania Stamataki
Marcelo Andrade De Lima
2Molecular & Structural Bioscience, School of Life Sciences, Keele University, Staffordshire, ST5 5BG, United Kingdom
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Jeremy E. Turnbull
4Copenhagen Center for Glycomics, Department of Cellular & Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen N 2200, Denmark
5Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, United Kingdom
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Zhang Yang
4Copenhagen Center for Glycomics, Department of Cellular & Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen N 2200, Denmark
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Elisa Vicenzi
3Viral Pathogenesis and Biosafety Unit, San Raffaele Scientific Institute, Via Olgettina, 58, Milano, Italy
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  • ORCID record for Elisa Vicenzi
Mark A. Skidmore
2Molecular & Structural Bioscience, School of Life Sciences, Keele University, Staffordshire, ST5 5BG, United Kingdom
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Farhat Khanim
6School of Biomedical Sciences, Institute for Clinical Sciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom
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  • For correspondence: a.richardson1@keele.ac.uk F.L.Khanim@bham.ac.uk
Alan Richardson
7School of Pharmacy and Bioengineering, Keele University, Staffordshire, ST5 5BG, United Kingdom
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  • ORCID record for Alan Richardson
  • For correspondence: a.richardson1@keele.ac.uk F.L.Khanim@bham.ac.uk
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Abstract

The SARS-CoV-2 pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure dimerization of ACE2, the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate. Fenofibric acid also destabilized the receptor binding domain (RBD) of the viral spike protein and inhibited RBD binding to ACE2 in ELISA and whole cell binding assays. Fenofibrate and fenofibric acid were tested by two independent laboratories measuring infection of cultured Vero cells using two different SARS-CoV-2 isolates. In both settings at drug concentrations which are clinically achievable, fenofibrate and fenofibric acid reduced viral infection by up to 70%. Together with its extensive history of clinical use and its relatively good safety profile, these studies identify fenofibrate as a potential therapeutic agent requiring urgent clinical evaluation to treat SARS-CoV-2 infection.

Teaser The approved drug fenofibrate inhibits infection by SARS-COV-2

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵# Joint last authors

  • Abbreviations

    Css
    steady-state plasma concentration
    Cmax
    maximum plasma concentration
    LgBIT
    Large binary interaction technology
    HiBIT
    High affinity binary interaction technology
    RBD
    Receptor binding domain
    ACE2
    Angiotensin converting enzyme 2
    SARS
    Severe acute respiratory syndrome
    ELISA
    Enzyme -linked immunosorbent assay
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    Posted January 11, 2021.
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    The hyperlipidaemic drug fenofibrate significantly reduces infection by SARS-CoV-2 in cell culture models
    Scott P. Davies, Courtney J. Mycroft-West, Isabel Pagani, Harriet J. Hill, Yen-Hsi Chen, Richard Karlsson, Ieva Bagdonaite, Scott E. Guimond, Zania Stamataki, Marcelo Andrade De Lima, Jeremy E. Turnbull, Zhang Yang, Elisa Vicenzi, Mark A. Skidmore, Farhat Khanim, Alan Richardson
    bioRxiv 2021.01.10.426114; doi: https://doi.org/10.1101/2021.01.10.426114
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    The hyperlipidaemic drug fenofibrate significantly reduces infection by SARS-CoV-2 in cell culture models
    Scott P. Davies, Courtney J. Mycroft-West, Isabel Pagani, Harriet J. Hill, Yen-Hsi Chen, Richard Karlsson, Ieva Bagdonaite, Scott E. Guimond, Zania Stamataki, Marcelo Andrade De Lima, Jeremy E. Turnbull, Zhang Yang, Elisa Vicenzi, Mark A. Skidmore, Farhat Khanim, Alan Richardson
    bioRxiv 2021.01.10.426114; doi: https://doi.org/10.1101/2021.01.10.426114

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