Linking COVID-19 and Heme-Driven Pathophysiologies: A Combined Computational–Experimental Approach
Marie-Thérèse Hopp,
Daniel Domingo-Fernández,
Yojana Gadiya,
Milena S. Detzel,
Regina Graf,
Benjamin F. Schmalohr,
Alpha T. Kodamullil,
Diana Imhof,
Martin Hofmann-Apitius
Affiliations
Marie-Thérèse Hopp
Pharmaceutical Biochemistry and Bioanalytics, Pharmaceutical Institute, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany
Daniel Domingo-Fernández
Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, D-53757 Sankt Augustin, Germany
Yojana Gadiya
Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, D-53757 Sankt Augustin, Germany
Milena S. Detzel
Pharmaceutical Biochemistry and Bioanalytics, Pharmaceutical Institute, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany
Regina Graf
Pharmaceutical Biochemistry and Bioanalytics, Pharmaceutical Institute, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany
Benjamin F. Schmalohr
Pharmaceutical Biochemistry and Bioanalytics, Pharmaceutical Institute, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany
Alpha T. Kodamullil
Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, D-53757 Sankt Augustin, Germany
Diana Imhof
Pharmaceutical Biochemistry and Bioanalytics, Pharmaceutical Institute, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany
Martin Hofmann-Apitius
Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, D-53757 Sankt Augustin, Germany
The SARS-CoV-2 outbreak was declared a worldwide pandemic in 2020. Infection triggers the respiratory tract disease COVID-19, which is accompanied by serious changes in clinical biomarkers such as hemoglobin and interleukins. The same parameters are altered during hemolysis, which is characterized by an increase in labile heme. We present two computational–experimental approaches aimed at analyzing a potential link between heme-related and COVID-19 pathophysiologies. Herein, we performed a detailed analysis of the common pathways induced by heme and SARS-CoV-2 by superimposition of knowledge graphs covering heme biology and COVID-19 pathophysiology. Focus was laid on inflammatory pathways and distinct biomarkers as the linking elements. In a second approach, four COVID-19-related proteins, the host cell proteins ACE2 and TMPRSS2 as well as the viral proteins 7a and S protein were computationally analyzed as potential heme-binding proteins with an experimental validation. The results contribute to the understanding of the progression of COVID-19 infections in patients with different clinical backgrounds and may allow for a more individual diagnosis and therapy in the future.
