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

人类胚胎干细胞衍生的心肌细胞平台筛选 SARS-CoV-2 感染的抑制剂

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作者: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

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 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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