Associate Professor Weill Cornell Medical College, New York, United States
hPSC-derived cells/organoids provide a platform to systematically evaluate the tropism and cellular response upon viral infection, which can be adapted to screen for anti-viral drugs. In response to the COVID-19 pandemic, we create a panel of hPSC-derived cells/organoids to study SARS-CoV-2 tropism. By screening ten different type of cells and organoids, we found that lung, colon, heart, liver, pancreatic organoids and dopamine neurons can be infected by SARS-CoV-2. This work presented the first stem cell model to understand the tropism of SARS-CoV-2, which led to a clinical trial to study beta cell function in COVID-19 patients. Furthermore, we reported the first organoid-based screen and identified several drug candidates blocking SARS-CoV-2 entry. One identified drug, imatinib, is currently being evaluated in several phase 2/3 clinical trials globally. Using this platform, we are screening the ReFRAME library for anti-SARS-CoV-2 drugs. Finally, we created an immune-host mini-heart tissue to model macrophage-mediated cardiomyocyte damage in COVID-19 patients. A high content screen using immune-host mini-heart tissue identified JAK inhibitor, which protects cardiomyocytes from macrophage-mediated damage upon SARS-CoV-2 infection.