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  • SARS-CoV-2 infection rewire...
    Mullen, Peter J; Garcia, Jr, 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

    Nature communications, 03/2021, Letnik: 12, Številka: 1
    Journal Article

    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.