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- Title
SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition.
- Authors
Mullen, Peter J.; Garcia, Gustavo; Purkayastha, Arunima; Matulionis, Nedas; Schmid, Ernst W.; Momcilovic, Milica; Sen, Chandani; Langerman, Justin; Ramaiah, Arunachalam; Shackelford, David B.; Damoiseaux, Robert; French, Samuel W.; Plath, Kathrin; Gomperts, Brigitte N.; Arumugaswami, Vaithilingaraja; Christofk, Heather R.
- Abstract
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.
- Subjects
SARS-CoV-2; CELL metabolism; COVID-19 treatment; COVID-19 pandemic; COVID-19
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-22166-4