Testing of clinically approved Camostat in preclinical human ex vivo lung culture model of SARS-CoV-2 infection

The SARS-CoV-2 triggered a pandemic of the "Coronavirus Disease-2019" (COVID-19). The viral entry of coronaviruses is based on binding of the viral spike protein (S protein) to cellular receptors and on S protein processing by host cell proteases. It is known that SARS-CoV-2 uses the human receptor ACE2 for cell entry and the serine protease TMPRSS2 for "priming" the S protein. The protease inhibitor Camostat, which has already been used clinically, reduces cell infection. So far, this has only been shown in cell lines or cell cultures that do not reflect the complexity of the three-dimensional alveolar lung cell association with type I, type II cells, endothelial cells and alveolar macrophages. The aim of the proposed project is to test Camostat in a preclinical model of human ex vivo lung cultures to better estimate the therapeutic potency of Camostat in COVID-19. The effects of Camostat in different doses at different times of infection of human ex vivo cultivated and infected with SARS-CoV-2 lung tissue are to be tested. Viral replication and the formation of interferons and selected pro-inflammatory cytokines are determined. These are the primary relevant readout parameters in an established model, supernatants and tissue are recorded in a biobank for follow-up analyzes. Depending on the findings, the experiments can be extended to other locally available relevant human ex vivo infection models of the upper respiratory tract (nasal turbinates, mucous membranes, sinuses, tonsils).