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| Status |
Public on Aug 11, 2020 |
| Title |
Identification of Drugs Blocking SARS-CoV-2 Infection using hPSC-derived Lung and Colonic Organoids |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The SARS-CoV-2 has already caused over twelve million COVID-19 cases and half a million deaths worldwide. 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. As SARS-CoV-2 primarily infects the respiratory tract, we developed a lung organoid model using human pluripotent stem cells (hPSC-LOs) that could be adapted for drug screening. The hPSC-LOs, particularly alveolar type II-like cells, express the viral entry receptor ACE2, are permissive to SARS-CoV-2 infection, and showed robust induction of chemokines and cytokines upon SARS-CoV-2 infection, similar to what is seen in COVID-19 patients. Nearly 25% of these patients have gastrointestinal manifestations, which are associated with worse COVID-19 outcomes1. We therefore also generated complementary hPSC-derived colonic organoids (hPSC-COs) to explore the response of colonic cells to SARS-CoV-2 infection. We found that multiple colonic cell types, especially enterocytes, express ACE2 and are permissive 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). Pre- or post-infection treatment at physiologically relevant levels of these drugs significantly inhibited SARS-CoV-2 infection of both hPSC-LOs and hPSC-COs. Together, these data demonstrate that hPSC-LOs and hPSC-COs infected by SARS-CoV-2 can serve as disease models to study SARS-CoV-2 infection and provide a valuable resource for drug screening to identify candidate COVID-19 therapeutics.
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| Overall design |
COVID-19 lung biopsy and SARS-CoV-2 infected lung organoids
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| Contributor(s) |
Han Y, Yang L, Chen S, Nilsson-Payant BE, Bram Y, Schwartz RE, tenOever BR |
| Citation(s) |
33116299 |
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| Submission date |
Jul 27, 2020 |
| Last update date |
Jan 05, 2022 |
| Contact name |
Shuibing Chen |
| E-mail(s) |
shuibing.chen@gmail.com
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| Phone |
2127465431
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| Organization name |
Weill Cornell Medical College
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| Department |
Surgery
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| Street address |
A 827B, 1300 York Ave
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (18)
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| GSM4697982 |
Healthy Lung autopsy [Healthy-lung] |
| GSM4697983 |
Healthy Lung autopsy_1 [HealthyLungBiopsy_1] |
| GSM4697984 |
Healthy Lung autopsy_2 [HealthyLungBiopsy_2] |
| GSM4697985 |
COVID_19 lung autopsy_1 [COVI19-Lung_59L-H1] |
| GSM4697986 |
COVID_19 lung autopsy_2 [COVI19-Lung_62L-H2] |
| GSM4697987 |
COVID_19 lung autopsy_3 [COVI19-Lung_64L-H3] |
| GSM4697988 |
hPSC_Lung organoid_mock_1 [2A] |
| GSM4697989 |
hPSC_Lung organoid_mock_2 [2B] |
| GSM4697990 |
hPSC_Lung organoid_mock_3 [2C] |
| GSM4697991 |
hPSC_Lung organoid_SARS-CoV-2_1 [2D] |
| GSM4697992 |
hPSC_Lung organoid_SARS-CoV-2_2 [2E] |
| GSM4697993 |
hPSC_Lung organoid_SARS-CoV-2_3 [2F] |
| GSM4718728 |
hPSC_Lung organoid_SARS-CoV-2_DMSO_1 [LungOrganoid-DMSO-1] |
| GSM4718729 |
hPSC_Lung organoid_SARS-CoV-2_DMSO_2 [LungOrganoid-DMSO-2] |
| GSM4718730 |
hPSC_Lung organoid_SARS-CoV-2_DMSO_3 [LungOrganoid-DMSO-3] |
| GSM4718731 |
hPSC_Lung organoid_SARS-CoV-2_imatinib_1 [LungOrganoid-10uM-Imatinib-1] |
| GSM4718732 |
hPSC_Lung organoid_SARS-CoV-2_imatinib_2 [LungOrganoid-10uM-Imatinib-2] |
| GSM4718733 |
hPSC_Lung organoid_SARS-CoV-2_imatinib_3 [LungOrganoid-10uM-Imatinib-3] |
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| Relations |
| BioProject |
PRJNA649019 |
| SRA |
SRP273808 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE155241_Processed_gene_expression.2.xlsx |
1.9 Mb |
(ftp)(http) |
XLSX |
| GSE155241_Processed_gene_expression.xlsx |
2.9 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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