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

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Williams, Thomas L 
Colzani, Maria T 
Bloor, Stuart 


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.



Antiviral Agents, Benztropine, Drug Evaluation, Preclinical, Human Embryonic Stem Cells, Humans, Myocytes, Cardiac, Peptides, SARS-CoV-2

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Commun Biol

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Springer Science and Business Media LLC
Wellcome Trust (107715/Z/15/Z)
British Heart Foundation (TG/18/4/33770)
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (203814/Z/16/Z)
Wellcome Trust (208363/Z/17/Z)
Wellcome Trust (210688/Z/18/Z)
British Heart Foundation (FS/18/46/33663)
British Heart Foundation (FS/17/61/33473D)
Medical Research Council (MC_PC_17230)
MRC (via University of Birmingham) (MR/V028448/1)
British Heart Foundation (None)
MRC (via University of Nottingham) (MC_PC_20060)
This research was funded in whole, or in part by: Wellcome Trust (WT107715/Z/15/Z, A.P.D., J.J.M.); Addenbrooke’s Charitable Trust (P.J.L., A.P.D.); Wellcome Trust Programme in Metabolic and Cardiovascular Disease (203814/Z/16/A, T.L.W., D.N.), Wellcome Trust Major Award (208363/Z/17/Z) for Imaging Core (G.S.); Wellcome Trust Principal Research Fellowship (210688/Z/18/Z, P.J.L.), UKRI/NIHR through the UK Coronavirus Immunology Consortium (P.J.L.); Rosetrees Trust Charity (G103718, J.R.Z.); British Heart Foundation (FS/17/61/33473 APD, S.S., R.G.C.M; TAF 03, APD, JJM); British Heart Foundation Senior Fellowship (FS/18/46/33663, S.S.), British Heart Foundation Centre for Regenerative Medicine (RM/17/2/33380, S.S., M.C.); Cambridge Biomedical Research Centre Biomedical Resources Grant (University of Cambridge, Cardiovascular Theme, RG64226) and a core support grant from the Wellcome Trust and MRC to the Wellcome–MRC Cambridge Stem Cell Institute.