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 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. Williams et al. confirm that human embryonic stem cell-derived cardiomyocytes express the protein machinery critical for SARS-CoV-2 infection and are susceptible to SARS-CoV-2 spike protein pseudotyped virus infection. They further use this platform as a screen to identify inhibitors of SARS-CoV-2 infection, reporting benztropine (targeting B0AT1/ACE2 complex) and DX600 (targeting ACE2) as potential inhibitors.

Automated summary

Patients with cardiovascular comorbidities are more vulnerable to severe infection with SARS-CoV-2, which can directly harm cardiovascular tissue. Researchers have developed a screening platform using human embryonic stem cell-derived cardiomyocytes to identify new inhibitors of SARS-CoV-2 infection, with benztropine and DX600 found as potential inhibitors. This discovery of new medicines is crucial for protecting the heart in SARS-CoV-2 patients and those who cannot be vaccinated.