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

Cell Death Dis. 2021 Aug 12;12(8):788. doi: 10.1038/s41419-021-03881-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Proteome
  • Viral Proteins
  • Viral Regulatory and Accessory Proteins