Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection

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 machiner...

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Autores principales: Williams, Thomas L., Colzani, Maria T., Macrae, Robyn G. C., Robinson, Emma L., Bloor, Stuart, Greenwood, Edward J. D., Zhan, Jun Ru, Strachan, Gregory, Kuc, Rhoda E., Nyimanu, Duuamene, Maguire, Janet J., Lehner, Paul J., Sinha, Sanjay, Davenport, Anthony P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322398/
https://www.ncbi.nlm.nih.gov/pubmed/34326460
http://dx.doi.org/10.1038/s42003-021-02453-y
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author Williams, Thomas L.
Colzani, Maria T.
Macrae, Robyn G. C.
Robinson, Emma L.
Bloor, Stuart
Greenwood, Edward J. D.
Zhan, Jun Ru
Strachan, Gregory
Kuc, Rhoda E.
Nyimanu, Duuamene
Maguire, Janet J.
Lehner, Paul J.
Sinha, Sanjay
Davenport, Anthony P.
author_facet Williams, Thomas L.
Colzani, Maria T.
Macrae, Robyn G. C.
Robinson, Emma L.
Bloor, Stuart
Greenwood, Edward J. D.
Zhan, Jun Ru
Strachan, Gregory
Kuc, Rhoda E.
Nyimanu, Duuamene
Maguire, Janet J.
Lehner, Paul J.
Sinha, Sanjay
Davenport, Anthony P.
author_sort Williams, Thomas L.
collection PubMed
description 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 SARS-CoV-2 spike-pseudotyped virus system. The method has allowed us to identify benztropine and DX600 as novel inhibitors of SARS-CoV-2 infection in a clinically relevant stem cell-derived cardiomyocyte line. Discovery of new medicines will be critical for protecting the heart in patients with SARS-CoV-2, and for individuals where vaccination is contraindicated.
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spelling pubmed-83223982021-08-03 Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection Williams, Thomas L. Colzani, Maria T. Macrae, Robyn G. C. Robinson, Emma L. Bloor, Stuart Greenwood, Edward J. D. Zhan, Jun Ru Strachan, Gregory Kuc, Rhoda E. Nyimanu, Duuamene Maguire, Janet J. Lehner, Paul J. Sinha, Sanjay Davenport, Anthony P. Commun Biol Article 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 SARS-CoV-2 spike-pseudotyped virus system. The method has allowed us to identify benztropine and DX600 as novel inhibitors of SARS-CoV-2 infection in a clinically relevant stem cell-derived cardiomyocyte line. Discovery of new medicines will be critical for protecting the heart in patients with SARS-CoV-2, and for individuals where vaccination is contraindicated. Nature Publishing Group UK 2021-07-29 /pmc/articles/PMC8322398/ /pubmed/34326460 http://dx.doi.org/10.1038/s42003-021-02453-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Williams, Thomas L.
Colzani, Maria T.
Macrae, Robyn G. C.
Robinson, Emma L.
Bloor, Stuart
Greenwood, Edward J. D.
Zhan, Jun Ru
Strachan, Gregory
Kuc, Rhoda E.
Nyimanu, Duuamene
Maguire, Janet J.
Lehner, Paul J.
Sinha, Sanjay
Davenport, Anthony P.
Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection
title Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection
title_full Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection
title_fullStr Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection
title_full_unstemmed Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection
title_short Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection
title_sort human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of sars-cov-2 infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322398/
https://www.ncbi.nlm.nih.gov/pubmed/34326460
http://dx.doi.org/10.1038/s42003-021-02453-y
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