Summary of Study ST001921
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001212. The data can be accessed directly via it's Project DOI: 10.21228/M81X3N This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST001921 |
| Study Title | An Airway Organoid-Based Screen Identifies a Role for the HIF1α-Glycolysis Axis in SARS-CoV-2 Infection |
| Study Summary | SARS-CoV-2 causes the COVID-19 pandemic. It is urgent to develop disease models to dissect mechanisms regulating SARS-CoV-2 infection. Here, we derive airway organoids from human pluripotent stem cells (hPSC-AOs). The hPSC-AOs, particularly ciliated-like cells, are permissive to SARS-CoV-2 infection. Using this platform, we perform a high content screen and identify GW6471, which blocks SARS-CoV-2 infection. GW6471 can also block infection of the B.1.351 SARS-CoV-2 variant. RNA-seq analysis suggests that GW6471 blocks SARS-CoV-2 infection at least in part by inhibiting HIF1α, which is further validated by chemical inhibitor and genetic perturbation targeting HIF1α. Metabolic profiling identifies decreased rates of glycolysis upon GW6471 treatment, consistent with transcriptome profiling. Finally, xanthohumol, 5-(Tetradecyloxy)-2-furoic acid, and ND-646, three compounds that suppress fatty acid biosynthesis, also block SARS-CoV-2 infection. Together, a high content screen coupled with transcriptome and metabolic profiling reveals a key role of the HIF1α-glycolysis axis in mediating SARS-CoV-2 infection of human airway epithelium. |
| Institute | Weill Cornell Medicine |
| Last Name | Chen |
| First Name | Shuibing |
| Address | A 827B, 1300 York Ave |
| shc2034@med.cornell.edu | |
| Phone | 2127465431 |
| Submit Date | 2021-09-24 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Waters) |
| Analysis Type Detail | GC-MS |
| Release Date | 2021-10-20 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO001992 |
| Collection Summary: | hPSC-AOs were collected into 150 mM ammonium acetate. After centrifugation, cell pellets were collected for metabolite profiling. Metabolite extraction was performed with 200 μl of 80% methanol (20% water) with internal standards (U13C succinate, and U13C citrate, and heptadecanoate). |
| Sample Type: | Lung organoids |
