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.
【저자키워드】 viral infection, Mucosal immunology, Mechanisms of disease, TOR signalling, 【초록키워드】 COVID-19, Treatment, SARS-CoV-2, Efficacy, therapy, SARS-COV-2 infection, lung, metabolism, kidney, Replication, viral replication, understanding, mTORC1, epithelial cells, inhibitor, expression, epithelial, change, patients, mechanism, Glucose, Glutamine, COVID-19 patients, Air-liquid interface, Evidence, cell lines, Potential treatment, COVID-19 patient, epithelial cell, evidence of, host cell, changes, Activation, pyruvate, potential treatments, lung tissue, cultures, cell line, carbon, TCA cycle, pandemic of COVID-19, block, Alter, oxidative, host cell metabolism, lung ALI cultures, caused, required, facilitate, increase, determine, suppresse, reduce, feasible, reduce viral replication, 【제목키워드】 susceptible,