In the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level, but the mechanisms of interaction between host and SARS-CoV-2, determining the grade of COVID-19 severity, are still unknown. We provide a network analysis on protein–protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred, applying an explorative algorithm (Random Walk with Restart, RWR) triggered by 28 proteins of SARS-CoV-2. The analysis of PPI allowed to estimate the distribution of SARS-CoV-2 proteins in the host cell. Interactome built around one single viral protein allowed to define a different response, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. Finally, the network-based approach highlighted a possible direct action of ORF3a and NS7b to enhancing Bradykinin Storm. This network-based representation of SARS-CoV-2 infection could be a framework for pathogenic evaluation of specific clinical outcomes. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients.
【저자키워드】 viral infection, Protein-protein interaction networks, 【초록키워드】 SARS-CoV-2, SARS-COV-2 infection, COVID-19 severity, cardiovascular disease, cardiovascular diseases, Viral proteins, host response, clinical outcomes, Protein, Viral, ORF3a, ORF8, bradykinin, Algorithm, phenotype, network analysis, interactome, proteome, distribution, mechanism, accessory protein, Protein–protein interaction, Interaction, Analysis, PPI, Pathways, protein–protein interactions, SARS-CoV-2 proteins, framework, host responses, GRADE, host cell, specific proteins, random walk, Viral protein, tissue, severe COVID-19 patients, host protein, pathogenic, SARS-CoV-2 protein, biological responses, restart, storm, pro-inflammatory, Host, approach, Cell, described, identify, to define, triggered, modulated, 【제목키워드】 pathway, pathogenic mechanism,