Summary of Study ST001709

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 PR001094. The data can be accessed directly via it's Project DOI: 10.21228/M89394 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	ST001709
Study Title	SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition
Study Summary	Viruses hijack host cell metabolism to acquire the building blocks required for viral replication. Understanding how SARS-CoV-2 alters host cell metabolism could lead to potential treatments for COVID-19, the disease caused by SARS-CoV-2 infection. Here we profile metabolic changes conferred by SARS-CoV-2 infection in kidney epithelial cells and lung air-liquid interface cultures and show that SARS-CoV-2 infection increases glucose carbon entry into the TCA cycle via increased pyruvate carboxylase expression. SARS-CoV-2 also reduces host cell oxidative glutamine metabolism while maintaining reductive carboxylation. Consistent with these changes in host cell metabolism, we show that SARS-CoV-2 increases activity of mTORC1, a master regulator of anabolic metabolism, in cell lines and patient lung stem cell-derived airway epithelial cells. We also show evidence of mTORC1 activation in COVID-19 patient lung tissue. Notably, mTORC1 inhibitors reduce viral replication in kidney epithelial cells and patient-derived lung stem cell cultures. This suggests that targeting mTORC1 could be a useful antiviral strategy for SARS-CoV-2 and treatment strategy for COVID-19 patients, although further studies are required to determine the mechanism of inhibition and potential efficacy in patients.
Institute	University of California, Los Angeles
Department	Biomedical Sciences
Laboratory	Heather Christofk
Last Name	Matulionis
First Name	Nedas
Address	615 Charles E Young Dr S, BSRB 354-05
Email	nmatulionis@mednet.ucla.edu
Phone	310-206-0163
Submit Date	2021-02-19
Raw Data Available	Yes
Raw Data File Type(s)	mzML
Analysis Type Detail	LC-MS
Release Date	2021-02-24
Release Version	1

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Sample Preparation:

Sampleprep ID:	SP001792
Sampleprep Summary:	To extract metabolites, we washed the cells with ice-cold 150 mM ammonium acetate, pH 7.3, and then added 500 uL 80% methanol and incubated for 20 minutes at -80°C. Cells were then scraped off the plate, vortexed and centrifuged for 10 minutes at maximum speed. We dried 400 uL of the supernatant under vacuum and stored the dried metabolites at -80°C. Dried metabolites were reconstituted in 100 µL of a 50% acetonitrile(ACN) 50% dH20 solution. Samples were vortexed and spun down for 10 min at 17,000g. 70 µL of the supernatant was then transferred to HPLC glass vials.

Sampleprep ID:

SP001792

Sampleprep Summary:

To extract metabolites, we washed the cells with ice-cold 150 mM ammonium acetate, pH 7.3, and then added 500 uL 80% methanol and incubated for 20 minutes at -80°C. Cells were then scraped off the plate, vortexed and centrifuged for 10 minutes at maximum speed. We dried 400 uL of the supernatant under vacuum and stored the dried metabolites at -80°C. Dried metabolites were reconstituted in 100 µL of a 50% acetonitrile(ACN) 50% dH20 solution. Samples were vortexed and spun down for 10 min at 17,000g. 70 µL of the supernatant was then transferred to HPLC glass vials.