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    A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics

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    Author
    Si, Longlong
    Bai, Haiqing
    Rodas, Melissa
    Cao, Wuji
    Oh, Crystal Yuri
    Jiang, Amanda
    Moller, Rasmus
    Hoagland, Daisy
    Oishi, Kohei
    Horiuchi, Shu
    Uhl, Skyler
    Blanco-Melo, Daniel
    Albrecht, Randy A
    Liu, Wen-Chun
    Jordan, Tristan
    Nilsson-Payant, Benjamin E
    Golynker, Ilona
    Frere, Justin
    Logue, James
    Haupt, Robert
    McGrath, Marisa
    Weston, Stuart
    Zhang, Tian
    Plebani, Roberto
    Soong, Mercy
    Nurani, Atiq
    Kim, Seong Min
    Zhu, Danni Y
    Benam, Kambez H
    Goyal, Girija
    Gilpin, Sarah E
    Prantil-Baun, Rachelle
    Gygi, Steven P
    Powers, Rani K
    Carlson, Kenneth E
    Frieman, Matthew
    tenOever, Benjamin R
    Ingber, Donald E
    Show allShow less

    Date
    2021-05-03
    Journal
    Nature Biomedical Engineering
    Publisher
    Springer Nature
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1038/s41551-021-00718-9
    Abstract
    The rapid repurposing of antivirals is particularly pressing during pandemics. However, rapid assays for assessing candidate drugs typically involve in vitro screens and cell lines that do not recapitulate human physiology at the tissue and organ levels. Here we show that a microfluidic bronchial-airway-on-a-chip lined by highly differentiated human bronchial-airway epithelium and pulmonary endothelium can model viral infection, strain-dependent virulence, cytokine production and the recruitment of circulating immune cells. In airway chips infected with influenza A, the co-administration of nafamostat with oseltamivir doubled the treatment-time window for oseltamivir. In chips infected with pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant doses of the antimalarial drug amodiaquine inhibited infection but clinical doses of hydroxychloroquine and other antiviral drugs that inhibit the entry of pseudotyped SARS-CoV-2 in cell lines under static conditions did not. We also show that amodiaquine showed substantial prophylactic and therapeutic activities in hamsters challenged with native SARS-CoV-2. The human airway-on-a-chip may accelerate the identification of therapeutics and prophylactics with repurposing potential.
    Keyword
    human airway-on-a-chip
    Antiviral Agents
    Drug Repositioning--methods
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/15665
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41551-021-00718-9
    Scopus Count
    Collections
    UMB Coronavirus Publications
    UMB Open Access Articles

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