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10.1038/s41467-021-22166-4

http://scihub22266oqcxt.onion/10.1038/s41467-021-22166-4
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33767183!7994801!33767183
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suck abstract from ncbi


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pmid33767183      Nat+Commun 2021 ; 12 (1): 1876
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  • SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition #MMPMID33767183
  • Mullen PJ; Garcia G Jr; Purkayastha A; Matulionis N; Schmid EW; Momcilovic M; Sen C; Langerman J; Ramaiah A; Shackelford DB; Damoiseaux R; French SW; Plath K; Gomperts BN; Arumugaswami V; Christofk HR
  • Nat Commun 2021[Mar]; 12 (1): 1876 PMID33767183show ga
  • 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.
  • |Animals[MESH]
  • |Benzamides/pharmacology[MESH]
  • |COVID-19/*pathology[MESH]
  • |Cell Line[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Citric Acid Cycle/*physiology[MESH]
  • |Glucose/metabolism[MESH]
  • |Glutamine/metabolism[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Lung/metabolism/virology[MESH]
  • |Mechanistic Target of Rapamycin Complex 1/*antagonists & inhibitors/*metabolism[MESH]
  • |Morpholines/pharmacology[MESH]
  • |Naphthyridines/pharmacology[MESH]
  • |Protein Kinase Inhibitors/*pharmacology[MESH]
  • |Pyrimidines/pharmacology[MESH]
  • |Pyruvate Carboxylase/biosynthesis[MESH]
  • |SARS-CoV-2/metabolism[MESH]
  • |Vero Cells[MESH]


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