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 |
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 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
Analysis ID | AN002783 | AN002784 |
---|---|---|
Analysis type | MS | MS |
Chromatography type | HILIC | HILIC |
Chromatography system | Thermo Vanquish | Thermo Vanquish |
Column | SeQuant ZIC-HILIC (150 x 2.1mm,5um) | SeQuant ZIC-HILIC (150 x 2.1mm,5um) |
MS Type | ESI | ESI |
MS instrument type | Orbitrap | Orbitrap |
MS instrument name | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap |
Ion Mode | POSITIVE | NEGATIVE |
Units | Peak Area | Peak Area |
Chromatography:
Chromatography ID: | CH002059 |
Chromatography Summary: | Samples were run on a Vanquish (Thermo Scientific) UHPLC system with mobile phase A (20 mM ammonium carbonate, pH 9.7) and mobile phase B (100% Acetonitrile) at a flow rate of 150 µL/min on a SeQuant ZIC-pHILIC Polymeric column (2.1 × 150 mm 5 μm, EMD Millipore) at 35°C. Separation was achieved with a linear gradient from 20% A to 80% A in 20 min followed by a linear gradient from 80% A to 20% A from 20 min to 20.5 min. 20% A was then held from 20.5 min to 28 min. |
Instrument Name: | Thermo Vanquish |
Column Name: | SeQuant ZIC-HILIC (150 x 2.1mm,5um) |
Column Temperature: | 35°C |
Flow Gradient: | 100% Acetonitrile |
Flow Rate: | 150 µL/min |
Internal Standard: | 10 nM Trifluoromethanesulfonate (extraction buffer) |
Solvent A: | 100% water; 20 mM ammonium carbonate, pH 9.7 |
Solvent B: | 100% acetonitrile |
Chromatography Type: | HILIC |