Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection
Thomas Williams, Maria Colzani, Robyn Macrae, Emma Robinson, Stuart Bloor, Edward JD Greenwood, Jun 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.