Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome

In the last months, many studies have clearly described several mechanisms of SARS−CoV−2 infection at cell and tissue level. Host conditions and comorbidities were identified as risk factors for severe and fatal disease courses, 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 on published PPI, using an explorative algorithm (Random Walk with Restart) triggered by all the 28 proteins of SARS−CoV−2, or each single viral protein one−by−one. The functional analysis for all proteins, linked to many aspects of COVID−19 pathogenesis, allows to identify the subcellular districts, where SARS−CoV−2 proteins seem to be distributed, while in each interactome built around one single viral protein, a different response was described, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. Finally, an explorative network-based approach was applied to Bradykinin Storm, highlighting a possible direct action of ORF3a and NS7b to enhancing this condition. This network-based model for 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.