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10.1016/j.molcel.2020.11.028

http://scihub22266oqcxt.onion/10.1016/j.molcel.2020.11.028
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33259812!7674017!33259812
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suck abstract from ncbi


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pmid33259812      Mol+Cell 2020 ; 80 (6): 1104-1122.e9
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  • Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2 #MMPMID33259812
  • Hekman RM; Hume AJ; Goel RK; Abo KM; Huang J; Blum BC; Werder RB; Suder EL; Paul I; Phanse S; Youssef A; Alysandratos KD; Padhorny D; Ojha S; Mora-Martin A; Kretov D; Ash PEA; Verma M; Zhao J; Patten JJ; Villacorta-Martin C; Bolzan D; Perea-Resa C; Bullitt E; Hinds A; Tilston-Lunel A; Varelas X; Farhangmehr S; Braunschweig U; Kwan JH; McComb M; Basu A; Saeed M; Perissi V; Burks EJ; Layne MD; Connor JH; Davey R; Cheng JX; Wolozin BL; Blencowe BJ; Wuchty S; Lyons SM; Kozakov D; Cifuentes D; Blower M; Kotton DN; Wilson AA; Muhlberger E; Emili A
  • Mol Cell 2020[Dec]; 80 (6): 1104-1122.e9 PMID33259812show ga
  • Human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative pathogen of the COVID-19 pandemic, exerts a massive health and socioeconomic crisis. The virus infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange, but the mechanisms driving infection and pathology are unclear. We performed a quantitative phosphoproteomic survey of induced pluripotent stem cell-derived AT2s (iAT2s) infected with SARS-CoV-2 at air-liquid interface (ALI). Time course analysis revealed rapid remodeling of diverse host systems, including signaling, RNA processing, translation, metabolism, nuclear integrity, protein trafficking, and cytoskeletal-microtubule organization, leading to cell cycle arrest, genotoxic stress, and innate immunity. Comparison to analogous data from transformed cell lines revealed respiratory-specific processes hijacked by SARS-CoV-2, highlighting potential novel therapeutic avenues that were validated by a high hit rate in a targeted small molecule screen in our iAT2 ALI system.
  • |Alveolar Epithelial Cells/*metabolism/pathology/virology[MESH]
  • |Animals[MESH]
  • |Antiviral Agents[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |COVID-19/genetics/*metabolism/pathology[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Cytopathogenic Effect, Viral[MESH]
  • |Cytoskeleton[MESH]
  • |Drug Evaluation, Preclinical[MESH]
  • |Humans[MESH]
  • |Induced Pluripotent Stem Cells/metabolism/pathology/virology[MESH]
  • |Phosphoproteins/genetics/*metabolism[MESH]
  • |Protein Transport[MESH]
  • |Proteome/genetics/*metabolism[MESH]
  • |SARS-CoV-2/genetics/*metabolism[MESH]
  • |Signal Transduction[MESH]


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