Analysis of SARS-CoV-2 infection in human lung organoids

Abstract: "Organoids are three dimensional tissues derived from stem cells. The usage of human induced pluripotent stem cells (iPSC) enables the differentiation into organoids with human tissue-like features. iPSC can also be used to differentiate human lung organoids (HLO). The organization of HLOs is similar to the native lung, e.g. these organoids contain upper airway-like epithelium with basal cells, immature ciliated cells, smooth muscle, myofibroblasts as well as alveolar-like cell types. Thus, HLOs offer an excellent model to study human lung diseases like COVID-19. Moreover, the iPS derived organoids overcome several of the limitations of currently used biopsy lung derived models (availability of alveolar epithelial type II cells (AT2), inter biopsy variance).Within this proposal we aim to elaborate basics for the establishment of a high-throughput approach (differentiate HLOs with low variance). HLOs will be characterized using cryo-sectioning and immunofluorescence analysis upon SARS-CoV-2 infection. We aim to study viral replication kinetics and host responses. We recently contributed to the establishment of the first reverse genetics system for SARS-CoV-2 offering the flexibility of using reporter viruses for a screening approach. Finally, we will test our system upon treatment with established antiviral compounds and aim to set up screening approaches to test antiviral compound libraries. Our approach offers a state-of-the-art model to study SARS-CoV-2 derived pathology and paves the way for the identification of effective antiviral drugs at high throughput level."; Research Type: discovery; Study population: not applicable