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Human embryonic stem cell-derived cardiomyocytes express SARS-CoV-2 host entry proteins: screen to identify inhibitors of infection

View ORCID ProfileThomas L. Williams, Maria T. Colzani, Robyn G.C. Macrae, View ORCID ProfileEmma L. Robinson, Stuart Bloor, Edward J. D. Greenwood, Jun Ru Zhan, Gregory Strachan, Rhoda E. Kuc, View ORCID ProfileDuuamene Nyimanu, View ORCID ProfileJanet J. Maguire, Paul J. Lehner, Sanjay Sinha, View ORCID ProfileAnthony P. Davenport
doi: https://doi.org/10.1101/2021.01.22.427737
Thomas L. Williams
1Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke’s Hospital, Cambridge, U.K.
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  • ORCID record for Thomas L. Williams
Maria T. Colzani
2Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, U.K.
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Robyn G.C. Macrae
1Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke’s Hospital, Cambridge, U.K.
2Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, U.K.
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Emma L. Robinson
3School of Medicine, Division of Cardiology, University of Colorado Denver, Anschutz Medical Campus, Aurora, U.S.A.
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  • ORCID record for Emma L. Robinson
Stuart Bloor
4Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, U.K.
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Edward J. D. Greenwood
4Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, U.K.
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Jun Ru Zhan
4Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, U.K.
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Gregory Strachan
5Wellcome Trust-MRC Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke’s Biomedical Campus, Cambridge, U.K.
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Rhoda E. Kuc
1Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke’s Hospital, Cambridge, U.K.
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Duuamene Nyimanu
1Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke’s Hospital, Cambridge, U.K.
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  • ORCID record for Duuamene Nyimanu
Janet J. Maguire
1Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke’s Hospital, Cambridge, U.K.
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  • ORCID record for Janet J. Maguire
Paul J. Lehner
4Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, U.K.
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Sanjay Sinha
2Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, U.K.
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  • For correspondence: ss661@cam.ac.uk apd10@medschl.cam.ac.uk
Anthony P. Davenport
1Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke’s Hospital, Cambridge, U.K.
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  • ORCID record for Anthony P. Davenport
  • For correspondence: ss661@cam.ac.uk apd10@medschl.cam.ac.uk
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Abstract

Patients with cardiovascular comorbidities are more susceptible to severe infection with SARS-CoV-2, known to directly cause pathological damage to cardiovascular tissue. We outline a screening platform using human embryonic stem cell-derived cardiomyocytes, confirmed to express the protein machinery critical for SARS-CoV-2 infection, and a pseudotyped virus system. The method has allowed us to identify benztropine and DX600 as novel inhibitors of SARS-CoV-2 infection.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 22, 2021.
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Human embryonic stem cell-derived cardiomyocytes express SARS-CoV-2 host entry proteins: screen to identify inhibitors of infection
Thomas L. Williams, Maria T. Colzani, Robyn G.C. Macrae, Emma L. Robinson, Stuart Bloor, Edward J. D. Greenwood, Jun Ru Zhan, Gregory Strachan, Rhoda E. Kuc, Duuamene Nyimanu, Janet J. Maguire, Paul J. Lehner, Sanjay Sinha, Anthony P. Davenport
bioRxiv 2021.01.22.427737; doi: https://doi.org/10.1101/2021.01.22.427737
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Human embryonic stem cell-derived cardiomyocytes express SARS-CoV-2 host entry proteins: screen to identify inhibitors of infection
Thomas L. Williams, Maria T. Colzani, Robyn G.C. Macrae, Emma L. Robinson, Stuart Bloor, Edward J. D. Greenwood, Jun Ru Zhan, Gregory Strachan, Rhoda E. Kuc, Duuamene Nyimanu, Janet J. Maguire, Paul J. Lehner, Sanjay Sinha, Anthony P. Davenport
bioRxiv 2021.01.22.427737; doi: https://doi.org/10.1101/2021.01.22.427737

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