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

Messina, F.; Giombini, E.; Montaldo, C.; Sharma, A. A.; Piacentini, M.; Zoccoli, A.; Sekaly, R. P.; Locatelli, F.; Zumla, A.; Maeurer, M.; Capobianchi, M. R.; Lauria, F. N.; Ippolito, G.

doi:10.1101/2020.11.03.366666

bioRxiv · 10.1101/2020.11.03.366666

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

Messina, F.·Giombini, E.·Montaldo, C.·Sharma, A. A.·Piacentini, M.·Zoccoli, A.·Sekaly, R. P.·Locatelli, F.·Zumla, A.·Maeurer, M.·Capobianchi, M. R.·Lauria, F. N.·Ippolito, G.

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Abstract

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.

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Messina, F., Giombini, E., Montaldo, C., Sharma, A. A., Piacentini, M., Zoccoli, A., Sekaly, R. P., Locatelli, F., Zumla, A., Maeurer, M., Capobianchi, M. R., Lauria, F. N., Ippolito, G.. 2020-11-03. Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome.. https://doi.org/10.1101/2020.11.03.366666

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