Kurzfassung

Since the beginning of 2020, the virus SARS-CoV-2 and its associated disease COVID-19 keep the world in suspense. Characterized by pneumonia and inflammation, COVID-19 can also lead to death in the most severe cases. After entry of the virus into the host cell via interaction of its S protein with ACE2, its replication and packaging in the host cell the virus finally enters the blood stream. There, virus particles are present in an even more complex environment with components from the three...Since the beginning of 2020, the virus SARS-CoV-2 and its associated disease COVID-19 keep the world in suspense. Characterized by pneumonia and inflammation, COVID-19 can also lead to death in the most severe cases. After entry of the virus into the host cell via interaction of its S protein with ACE2, its replication and packaging in the host cell the virus finally enters the blood stream. There, virus particles are present in an even more complex environment with components from the three major regulating systems, the immune, the complement and the coagulation system. Several important clinical parameters, such as the values for hemoglobin and albumin, or inflammation markers are thus changed in COVID-19 patients. Interestingly, the same changes are monitored in hemolytic conditions, which, in addition, are accompanied by an excess of released heme. Inspired by our recent preliminary results, the aim of this project is to analyze the potential link between labile heme and COVID- 19 pathophysiology in more detail. Two approaches are to be pursued for this purpose. On the one hand, a potential binding of heme to selected COVID-19-relevant proteins, namely ACE2, protein 7a, S protein and TMPRSS2, will be characterized by in vitro binding studies, such as via UV/Vis and SPR spectroscopy, as well as by in silico approaches. On the other hand, the potential correlation of COVID-19 infection and labile heme will be further investigated with the incorporation of new clinical data in the recently published COVID-19 knowledge graph, which will allow for a more detailed characterization of the potential relationship between COVID-19 and heme pathophysiology. In the future, information gained from these two approaches may help to understand criteria, which lead to COVID-19 depending on the pre(existing) conditions and clinical background of the patients, while others are not affected. This, in turn, will specifically support diagnostics and treatment options for SARS-CoV-2 infections.» weiterlesen» einklappen