02613nas a2200421   4500000000100000000000100001008004100002260001500043653002700058653002000085100001500105700001400120700001700134700001500151700001500166700001500181700001600196700001500212700001800227700001500245700001600260700001800276700001100294700001500305700002000320700002200340700002100362700001900383700001700402700001800419700002100437245013500458856005500593300001000648490000700658520151200665022001402177       2021                            d  c2021-07-2210aBiomedical Engineering10aViral infection1 aA. L. Gard1 aR. J. Luu1 aC. R. Miller1 aR. Maloney1 aB. P. Cain1 aE. E. Marr1 aD. M. Burns1 aR. Gaibler1 aT. J. Mulhern1 aC. A. Wong1 aJ. Alladina1 aJ. R. Coppeta1 aP. Liu1 aJ. P. Wang1 aH. Azizgolshani1 aR. Fennell Fezzie1 aJ. L. Balestrini1 aB. C. Isenberg1 aB. D. Medoff1 aR. W. Finberg1 aJ. T. Borenstein00aHigh-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro  uhttps://www.nature.com/articles/s41598-021-94095-7  a149610 v113 aInfluenza 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.  a2045-2322