Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome
biorxiv(2020)
摘要
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.
### Competing Interest Statement
The authors have declared no competing interest.
* PPI
: Protein-Protein Interactions
SARS-CoV
: Severe Acute Respiratory Syndrome Coronavirus
SARS-CoV-2
: Severe Acute Respiratory Syndrome Coronavirus 2
H-CoV
: Human Coronavirus
COVID-19
: Coronavirus Disease 19
ORF
: Open Reading Frame
RWR
: Random walk with restart
FDR
: False Discovery Rate
ER
: Endoplasmic reticulum
Nsp
: non-structural protein
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关键词
pathogenic mechanisms,host interactome,pathways,sars-cov
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