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10.1038/s41598-021-94095-7

http://scihub22266oqcxt.onion/10.1038/s41598-021-94095-7
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suck abstract from ncbi


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pmid34294757      Sci+Rep 2021 ; 11 (1): 14961
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  • High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro #MMPMID34294757
  • Gard AL; Luu RJ; Miller CR; Maloney R; Cain BP; Marr EE; Burns DM; Gaibler R; Mulhern TJ; Wong CA; Alladina J; Coppeta JR; Liu P; Wang JP; Azizgolshani H; Fezzie RF; Balestrini JL; Isenberg BC; Medoff BD; Finberg RW; Borenstein JT
  • Sci Rep 2021[Jul]; 11 (1): 14961 PMID34294757show ga
  • Influenza and other respiratory viruses present a significant threat to public health, national security, and the world economy, and can lead to the emergence of global pandemics such as from COVID-19. A barrier to the development of effective therapeutics is the absence of a robust and predictive preclinical model, with most studies relying on a combination of in vitro screening with immortalized cell lines and low-throughput animal models. Here, we integrate human primary airway epithelial cells into a custom-engineered 96-device platform (PREDICT96-ALI) in which tissues are cultured in an array of microchannel-based culture chambers at an air-liquid interface, in a configuration compatible with high resolution in-situ imaging and real-time sensing. We apply this platform to influenza A virus and coronavirus infections, evaluating viral infection kinetics and antiviral agent dosing across multiple strains and donor populations of human primary cells. Human coronaviruses HCoV-NL63 and SARS-CoV-2 enter host cells via ACE2 and utilize the protease TMPRSS2 for spike protein priming, and we confirm their expression, demonstrate infection across a range of multiplicities of infection, and evaluate the efficacy of camostat mesylate, a known inhibitor of HCoV-NL63 infection. This new capability can be used to address a major gap in the rapid assessment of therapeutic efficacy of small molecules and antiviral agents against influenza and other respiratory viruses including coronaviruses.
  • |Antiviral Agents/*pharmacology[MESH]
  • |Bronchi/cytology/virology[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |COVID-19/virology[MESH]
  • |Cell Culture Techniques/instrumentation[MESH]
  • |Cell Line[MESH]
  • |Coronavirus Infections/drug therapy/*virology[MESH]
  • |Coronavirus/drug effects[MESH]
  • |Equipment Design[MESH]
  • |High-Throughput Screening Assays/instrumentation[MESH]
  • |Humans[MESH]
  • |Influenza A virus/drug effects[MESH]
  • |Influenza, Human/drug therapy/*virology[MESH]
  • |Microbial Sensitivity Tests/*instrumentation[MESH]
  • |Microfluidic Analytical Techniques/*instrumentation[MESH]
  • |Respiratory Mucosa/*cytology/virology[MESH]
  • |Respiratory Tract Infections/drug therapy/virology[MESH]


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