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

Apoorva Mulay | Zendy; Bindu Konda | Zendy; Gustavo Garcia | Zendy; Changfu Yao | Zendy; Stephen Beil | Zendy; Jaquelyn M. Villalba | Zendy; Colin Koziol | Zendy; Chandani Sen | Zendy; Arunima Purkayastha | Zendy; Jay K. Kolls | Zendy; Derek Pociask | Zendy; Patrizia Pessina | Zendy; Julio Sainz de Aja | Zendy; Carolina García de Alba | Zendy; Carla F. Kim | Zendy; Brigitte N. Gomperts | Zendy; Vaithilingaraja Arumugaswami | Zendy; Barry R. Stripp | Zendy

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

Author(s) -

Apoorva Mulay,

Bindu Konda,

Gustavo Garcia,

Changfu Yao,

Stephen Beil,

Jaquelyn M. Villalba,

Colin Koziol,

Chandani Sen,

Arunima Purkayastha,

Jay K. Kolls,

Derek Pociask,

Patrizia Pessina,

Julio Sainz de Aja,

Carolina García de Alba,

Carla F. Kim,

Brigitte N. Gomperts,

Vaithilingaraja Arumugaswami,

Barry R. Stripp

Publication year - 2021

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2021.109055

Subject(s) - lung , respiratory epithelium , epithelium , immunology , proinflammatory cytokine , interferon , virology , respiratory system , coronavirus , biology , medicine , inflammation , covid-19 , disease , pathology , infectious disease (medical specialty)

Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). While infection initiates in the proximal airways, severe and sometimes fatal symptoms of the disease are caused by infection of the alveolar type 2 (AT2) cells of the distal lung and associated inflammation. In this study we develop primary human lung epithelial infection models to understand initial responses of proximal and distal lung epithelium to SARS-CoV-2 infection. Differentiated air-liquid interface (ALI) cultures of proximal airway epithelium and alveosphere cultures of distal lung AT2 cells are readily infected by SARS-CoV-2, leading to an epithelial cell-autonomous proinflammatory response with increased expression of interferon signaling genes. Studies to validate the efficacy of selected candidate COVID-19 drugs confirm that Remdesivir strongly suppresses viral infection/replication. We provide a relevant platform for study of COVID-19 pathobiology and for rapid drug screening against SARS-CoV-2 and emergent respiratory pathogens.

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