1. Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection
- Author
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Robyn Macrae, Paul J. Lehner, Sanjay Sinha, Stuart Bloor, Thomas L Williams, Jun Ru Zhan, Janet J. Maguire, Edward J. D. Greenwood, Duuamene Nyimanu, Maria Colzani, Emma L Robinson, Rhoda E. Kuc, Gregory Strachan, Anthony P. Davenport, Macrae, Robyn GC [0000-0002-8129-7242], Robinson, Emma L [0000-0002-4866-731X], Greenwood, Edward JD [0000-0002-5224-0263], Strachan, Gregory [0000-0002-3554-5401], Lehner, Paul J [0000-0001-9383-1054], Sinha, Sanjay [0000-0001-5900-1209], Davenport, Anthony P [0000-0002-2096-3117], Apollo - University of Cambridge Repository, Macrae, Robyn G. C. [0000-0002-8129-7242], Robinson, Emma L. [0000-0002-4866-731X], Greenwood, Edward J. D. [0000-0002-5224-0263], Lehner, Paul J. [0000-0001-9383-1054], Davenport, Anthony P. [0000-0002-2096-3117], Macrae, Robyn G C [0000-0002-8129-7242], and Greenwood, Edward J D [0000-0002-5224-0263]
- Subjects
0301 basic medicine ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,QH301-705.5 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,viruses ,Human Embryonic Stem Cells ,Drug Evaluation, Preclinical ,Medicine (miscellaneous) ,631/532/2440 ,Bioinformatics ,14 ,Antiviral Agents ,General Biochemistry, Genetics and Molecular Biology ,Virus ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,In patient ,Myocytes, Cardiac ,Biology (General) ,14/19 ,skin and connective tissue diseases ,health care economics and organizations ,Pharmacology ,Benztropine ,631/154/436 ,business.industry ,SARS-CoV-2 ,fungi ,article ,Embryonic stem cell ,3. Good health ,respiratory tract diseases ,Vaccination ,body regions ,030104 developmental biology ,General Agricultural and Biological Sciences ,business ,Peptides ,Heart stem cells ,030217 neurology & neurosurgery - 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., 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.
- Published
- 2021