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dc.contributor.authorSi, Longlong
dc.contributor.authorBai, Haiqing
dc.contributor.authorRodas, Melissa
dc.contributor.authorCao, Wuji
dc.contributor.authorOh, Crystal Yuri
dc.contributor.authorJiang, Amanda
dc.contributor.authorMoller, Rasmus
dc.contributor.authorHoagland, Daisy
dc.contributor.authorOishi, Kohei
dc.contributor.authorHoriuchi, Shu
dc.contributor.authorUhl, Skyler
dc.contributor.authorBlanco-Melo, Daniel
dc.contributor.authorAlbrecht, Randy A
dc.contributor.authorLiu, Wen-Chun
dc.contributor.authorJordan, Tristan
dc.contributor.authorNilsson-Payant, Benjamin E
dc.contributor.authorGolynker, Ilona
dc.contributor.authorFrere, Justin
dc.contributor.authorLogue, James
dc.contributor.authorHaupt, Robert
dc.contributor.authorMcGrath, Marisa
dc.contributor.authorWeston, Stuart
dc.contributor.authorZhang, Tian
dc.contributor.authorPlebani, Roberto
dc.contributor.authorSoong, Mercy
dc.contributor.authorNurani, Atiq
dc.contributor.authorKim, Seong Min
dc.contributor.authorZhu, Danni Y
dc.contributor.authorBenam, Kambez H
dc.contributor.authorGoyal, Girija
dc.contributor.authorGilpin, Sarah E
dc.contributor.authorPrantil-Baun, Rachelle
dc.contributor.authorGygi, Steven P
dc.contributor.authorPowers, Rani K
dc.contributor.authorCarlson, Kenneth E
dc.contributor.authorFrieman, Matthew
dc.contributor.authortenOever, Benjamin R
dc.contributor.authorIngber, Donald E
dc.date.accessioned2021-05-17T15:16:30Z
dc.date.available2021-05-17T15:16:30Z
dc.date.issued2021-05-03
dc.identifier.urihttp://hdl.handle.net/10713/15665
dc.description.abstractThe 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.en_US
dc.description.urihttps://doi.org/10.1038/s41551-021-00718-9en_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofNature Biomedical Engineeringen_US
dc.subjecthuman airway-on-a-chipen_US
dc.subject.meshAntiviral Agentsen_US
dc.subject.meshDrug Repositioning--methodsen_US
dc.titleA human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylacticsen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41551-021-00718-9
dc.identifier.pmid33941899
dc.source.countryEngland


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