SARS-CoV-2 infection of primary human lung epithelium for COVID-19 modeling and drug discovery

Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic resulting from zoonotic transmission of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Severe symptoms include viral pneumonia secondary to infection and inflammation of the lower respiratory tract, in some...

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Bibliographic Details
Published in:bioRxiv 2020-06
Main Authors: Mulay, A, Konda, B, Garcia, Jr, G, Yao, C, Beil, S, Sen, C, Purkayastha, A, Kolls, J K, Pociask, D A, Pessina, P, de Aja, J Sainz, Garcia-de-Alba, C, Kim, C F, Gomperts, B, Arumugaswami, V, Stripp, B R
Format: Article
Language:English
Subjects:
Alveoli
Coronaviruses
COVID-19
Disease transmission
Drug development
Drug screening
Epithelial cells
Epithelium
Infections
Inflammation
Organoids
Pandemics
Respiratory diseases
Respiratory tract
Severe acute respiratory syndrome coronavirus 2
Viral infections
Zoonoses
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Summary:Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic resulting from zoonotic transmission of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Severe symptoms include viral pneumonia secondary to infection and inflammation of the lower respiratory tract, in some cases causing death. We developed primary human lung epithelial infection models to understand responses of proximal and distal lung epithelium to SARS-CoV-2 infection. Differentiated air-liquid interface cultures of proximal airway epithelium and 3D organoid cultures of alveolar epithelium were readily infected by SARS-CoV-2 leading to an epithelial cell-autonomous proinflammatory response. We validated the efficacy of selected candidate COVID-19 drugs confirming that Remdesivir strongly suppressed viral infection/replication. We provide a relevant platform for studying COVID-19 pathobiology and for rapid drug screening against SARS-CoV-2 and future emergent respiratory pathogens. A novel infection model of the adult human lung epithelium serves as a platform for COVID-19 studies and drug discovery.
ISSN:2692-8205
2692-8205
DOI:10.1101/2020.06.29.174623