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

BioRxiv : the Preprint Server for Biology
A. MulayBarry Stripp

Abstract

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.

Citations

Aug 21, 2020·Mucosal Immunology·M D JohansenP M Hansbro
Dec 10, 2020·CPT: Pharmacometrics & Systems Pharmacology·Patrick O HanafinGauri G Rao
Jan 15, 2021·Clinical Microbiology Reviews·Aleksandra SynowiecKrzysztof Pyrc
Jan 13, 2021·Cells·Rishi Man ChughSubhrajit Saha
May 25, 2021·Current Opinion in Pharmacology·Sonia YouhannaVolker M Lauschke

Datasets Mentioned

BETA
MT246667.1

Methods Mentioned

BETA
scraping
fluorescence associated cell sorting
FACS
PCR
biopsies
chip
confocal microscopy
RNA seq

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

American Thoracic Society: Allergy, Immunology & Inflammation

This feed has been developed in conjunction with the American Thoracic Society for the benefit of its Allergy, Immunology, and Inflammation Assembly. It highlights new and impactful papers on allergy, asthma, genetics, and the pathogenesis of lung diseases.