Looking for pathways related to COVID-19: confirmation of pathogenic mechanisms by SARS-CoV-2-host interactome.

Abstract

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.

• Authors: Francesco Messina, Emanuela Giombini, Chiara Montaldo, Ashish Arunkumar Sharma, Antonio Zoccoli, Rafick-Pierre Sekaly, Franco Locatelli, Alimuddin Zumla, Markus Maeurer, Maria R Capobianchi, Francesco Nicola Lauria, Giuseppe Ippolito
• Journal: Cell death & disease (Cell Death Dis) Vol. 12 Issue 8 Pg. 788 (08 12 2021) ISSN: 2041-4889 [Electronic] England
• PMID: 34385425 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Proteome
• Viral Proteins
• Viral Regulatory and Accessory Proteins

Topics

• COVID-19 (metabolism, virology)
• Host Microbial Interactions
• Immunity (immunology)
• Protein Interaction Maps (physiology)
• Proteome
• Proteomics (methods)
• SARS-CoV-2 (metabolism, pathogenicity)
• Severity of Illness Index
• Viral Proteins (metabolism)
• Viral Regulatory and Accessory Proteins (metabolism)