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.

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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.

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Study IDST001921
Study TitleAn Airway Organoid-Based Screen Identifies a Role for the HIF1α-Glycolysis Axis in SARS-CoV-2 Infection
Study SummarySARS-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 NameChen
First NameShuibing
AddressA 827B, 1300 York Ave
Emailshc2034@med.cornell.edu
Phone2127465431
Submit Date2021-09-24
Raw Data AvailableYes
Raw Data File Type(s)raw(Waters)
Analysis Type DetailGC-MS
Release Date2021-10-20
Release Version1
Shuibing Chen Shuibing Chen
https://dx.doi.org/10.21228/M81X3N
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Sample Preparation:

Sampleprep ID:SP002005
Sampleprep Summary:In brief, the samples were methoximized with 50 µl of methoxyamine hydrochloride (MOA, 15 mg/mL in pyridine) at 30°C for 90 minutes. The silylation step was done with 50 µl of N,O-Bis(trimethylsilyl)trifluoroacetamide (BSTFA, containing 1% TMCS, Supelco, PA, USA) at 70 °C for 60 minutes. After the samples cooled to room temperature, they were analyzed by GC-TOF/MS. Separation was performed with a 30-meter DB-5MS column coupled with 10-meter guard column. Helium was used as carrier gas at a flow of 1 ml/min. The oven program is as the following: started at 60 °C for 1 minute, 10°C /min to 320 minutes and kept for 3 minutes.
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