Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV

Area of Science:

• Virology
• Molecular Biology
• Systems Biology

Background:

• The global spread of SARS-CoV-2 necessitates understanding viral protein functions and host interactions.
• Previous omics studies provided fragmented insights into COVID-19 pathophysiology.
• Integrating diverse omics data for a holistic view of virus-host interactions is challenging due to experimental system heterogeneity.

Purpose of the Study:

• To conduct a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV.
• To profile viral interactomes and their impact on host cell systems.
• To identify common and distinct molecular mechanisms of these coronaviruses.

Main Methods:

• Concurrent multi-omics profiling (proteomics, transcriptomics, ubiquitinomics, phosphoproteomics) of a human lung cell line infected with SARS-CoV-2 and SARS-CoV.
• Interactome profiling of both viruses.
• Network analysis to project multi-omics data onto cellular interaction networks.

Main Results:

• Comprehensive interactomes for SARS-CoV-2 and SARS-CoV were profiled.
• Virus-induced perturbations were analyzed across multiple molecular layers (transcriptome, proteome, ubiquitinome, phosphoproteome).
• Specific dysregulation of the TGF-β pathway by SARS-CoV-2 ORF8 and autophagy by SARS-CoV-2 ORF3 was identified.
• Network analysis revealed crosstalk and distinct/common molecular mechanisms between SARS-CoV-2 and SARS-CoV infections.
• Potential drug targets, including kinase and matrix metalloprotease inhibitors, were identified with potent antiviral effects.

Conclusions:

• The study provides an integrated multi-omics dataset for understanding SARS-CoV-2 and SARS-CoV pathogenesis.
• Distinct and common molecular mechanisms employed by these viruses were elucidated.
• The findings highlight potential therapeutic strategies, including targeting specific pathways and identifying existing drugs with antiviral activity.