Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-22166-4
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Funding
- UCLA David Geffen School of Medicine-Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Award Program
- NIH National Center for Advancing Translational Science (NCATS) UCLA CTSI [UL1TR001881]
- Broad Stem Cell Research Center institutional award (OCRC) [20-1]
- California Institute for Regenerative Medicine Discovery Award [DISC2COVID19-11764]
- NIH [U2C-DK119886]
- UCLA DGSOM
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This study revealed that SARS-CoV-2 infection alters host cell metabolism by increasing glucose entry into the TCA cycle and reducing oxidative glutamine metabolism. Additionally, infection with SARS-CoV-2 activates mTORC1, and inhibiting mTORC1 can suppress viral replication in kidney epithelial cells and lung ALI cultures. These findings suggest that targeting mTORC1 could be a potential treatment strategy for COVID-19 patients.
Viruses hijack host cell metabolism to acquire the building blocks required for replication. Understanding how SARS-CoV-2 alters host cell metabolism may lead to potential treatments for COVID-19. Here we profile metabolic changes conferred by SARS-CoV-2 infection in kidney epithelial cells and lung air-liquid interface (ALI) 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 oxidative glutamine metabolism while maintaining reductive carboxylation. Consistent with these changes, SARS-CoV-2 infection increases the activity of mTORC1 in cell lines and lung ALI cultures. Lastly, we show evidence of mTORC1 activation in COVID-19 patient lung tissue, and that mTORC1 inhibitors reduce viral replication in kidney epithelial cells and lung ALI cultures. Our results suggest that targeting mTORC1 may be a feasible treatment strategy for COVID-19 patients, although further studies are required to determine the mechanism of inhibition and potential efficacy in patients. The pandemic of COVID-19, caused by SARS-CoV-2 infection, warrants immediate investigation for therapy options. Here the authors show, using epithelial and air-liquid interface cultures, that SARS-CoV-2 hijacks host cell metabolism to facilitate viral replication, and that inhibition of mTORC1, a master metabolic regulator, suppresses viral replication.
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