Putting SARS-CoV-2 where it belongs: Identification of potential therapeutic targets with single cell analysis

Available On Demand

Respiratory failure is the most common adverse outcome for COVID-19 patients, but scientists and doctors are still searching for answers to the clinical complications of SARS-CoV-2 infection arising in other organs in the body, including the metabolic, cardiac, neurological, and gastrointestinal systems. Moreover, studies of SARS-CoV-2 infection mechanisms have relied on ACE2-overexpressing cells, masking the potential role of other factors in viral entry. Thus, there is an urgent need to create novel models using human disease-relevant cells to study SARS-CoV-2 biology and to facilitate drug screening.

In this webinar, we discuss efforts to develop a lung organoid model using human pluripotent stem cells (hPSC-LOs) to inform our understanding of SARS-CoV-2 infection and the immune response in both a physiologically relevant context and in specific lung cell types. We also generated complementary hPSC-derived colonic organoids (hPSC-COs) to explore the response of colonic cells to SARS-CoV-2 infection. Using hPSC-LOs, we performed a high throughput screen of FDA-approved drugs and identified entry inhibitors of SARS-CoV-2, including imatinib, mycophenolic acid (MPA), and quinacrine dihydrochloride (QNHC). Treatment at physiologically relevant levels of these drugs significantly inhibited SARS-CoV-2 infection of both hPSC-LOs and hPSC-COs.

What you will learn: 

* Human pluripotent stem cell-derived colon and lung organoids provide useful models to study SARS-CoV-2 infection in a physiologically relevant context.

* 10x Genomics single cell RNA-sequencing is a powerful tool to identify cell–type specific susceptibility to SARS-CoV-2 infection in complex colon and lung organoids.

* Single cell analysis of hPSC-LOs and hPSC-COs infected by SARS-CoV-2, in conjunction with high throughput drug screening, can accelerate identification of candidate COVID-19 therapeutics.

Shuibing Chen, PhD
Associate Professor of Chemical Biology
Cornell Medicine, New York
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Alejandro Montenegro-Montero, PhD
Current Protocols
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