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.
【저자키워드】 viral infection, biomedical engineering, 【초록키워드】 COVID-19, public health, SARS-CoV-2, Efficacy, ACE2, Coronaviruses, Antiviral, Influenza, Human, Infection, influenza A virus, Camostat mesylate, animal models, in vitro, Population, Spike protein, Coronavirus infections, Culture, Pandemics, small molecule, antiviral agent, inhibitor, expression, platform, Donor, HCoV-NL63, Combination, strain, Predictive, host cell, tissue, therapeutic efficacy, priming, protease TMPRSS2, National, air–liquid interface, effective, robust, evaluate, can be used, coronavirus, absence, other respiratory virus, airway epithelial cell, human primary cells, immortalized cell line, 【제목키워드】 coronavirus, Influenza, in vitro, airway, other respiratory virus,