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Updated: Sep 20, 2025

A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
13:56

A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions

Published on: July 18, 2013

11.3K

A comprehensive SARS-CoV-2-human protein-protein interactome network identifies pathobiology and host-targeting

Yadi Zhou1, Yuan Liu2, Shagun Gupta2,3

  • 1Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, US.

Research Square
|June 9, 2022
PubMed

Insights

This study maps SARS-CoV-2 protein interactions with human cells, identifying 739 interactions and discovering carvedilol as a potential COVID-19 treatment. Carvedilol shows antiviral activity and is linked to reduced positive test rates in patients.

Area of Science:

  • Virology
  • Systems Biology
  • Drug Discovery

Background:

  • Viral-host protein-protein interactions are critical for viral replication and host immune responses, making them key targets for therapeutic strategies.
  • Understanding the comprehensive SARS-CoV-2-human interactome is essential for identifying novel drug targets and treatment interventions.

Approach:

  • Generated a high-confidence SARS-CoV-2-human protein-protein interaction network using yeast two-hybrid and mass spectrometry.
  • Identified 739 high-confidence interactions, demonstrating significant overlap with existing datasets and differentially expressed genes in COVID-19 patients.
  • Performed network-based drug screening of over 2,900 drugs to identify compounds targeting SARS-CoV-2 host factors.

Key Points:

  • Discovered a novel interaction between SARS-CoV-2 ORF3a and host ZNF579, highlighting a mechanism for viral impact on host transcription.
  • Identified 23 potential drugs, including carvedilol, with significant network proximity to SARS-CoV-2 host factors.
  • Carvedilol demonstrated antiviral activity in vitro and was associated with a reduced likelihood of SARS-CoV-2 positivity in electronic health records.

Conclusions:

  • Large-scale network systems biology approaches are valuable for biological insight extraction and identifying therapeutic candidates.
  • The identified SARS-CoV-2-human interactome provides a resource for further research into viral pathogenesis and drug development.
  • Carvedilol shows promise as a repurposed drug for COVID-19 treatment, warranting further clinical investigation.

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