A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics
Author
Si, LonglongBai, 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
Date
2021-05-03Journal
Nature Biomedical EngineeringPublisher
Springer NatureType
Article
Metadata
Show full item recordAbstract
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.Identifier to cite or link to this item
http://hdl.handle.net/10713/15665ae974a485f413a2113503eed53cd6c53
10.1038/s41551-021-00718-9
Scopus Count
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