01871nas a2200301   4500000000100000000000100001008004100002260001500043100001300058700001300071700001400084700001100098700001200109700001100121700001900132700001600151700001800167700001500185700002000200700002200220700001400242700001600256700002000272700001700292245009900309300002200408520113900430       2020                            d  c2020-06-291 aA. Mulay1 aB. Konda1 aG. Garcia1 aC. Yao1 aS. Beil1 aC. Sen1 aA. Purkayastha1 aJ. K. Kolls1 aD. A. Pociask1 aP. Pessina1 aJ. Sainz de Aja1 aC. Garcia-de-Alba1 aC. F. Kim1 aB. Gomperts1 aV. Arumugaswami1 aB. R. Stripp00aSARS-CoV-2 infection of primary human lung epithelium for COVID-19 modeling and drug discovery  a2020.06.29.1746233 aCoronavirus 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.
ONE SENTENCE SUMMARY: A novel infection model of the adult human lung epithelium serves as a platform for COVID-19 studies and drug discovery.