Ectopic expression of SARS-CoV-2 S and ORF-9B proteins alters metabolic profiles and impairs contractile function in

Peng Zhang1, Yu Liu2, Chunfeng Li3

  • 1Department of Biological Sciences, Clemson University, Clemson, SC, United States.

Insights

The SARS-CoV-2 S and ORF-9B viral subunits impair heart cell function and metabolism. This study reveals mechanisms of COVID-19 cardiac complications, offering insights into viral impacts on the cardiovascular system.

Area of Science:

  • Cardiovascular Science
  • Molecular Biology
  • Virology

Background:

  • Coronavirus disease 2019 (COVID-19) presents cardiovascular complications.
  • The precise molecular mechanisms underlying these cardiac impacts remain largely unknown.

Purpose of the Study:

  • To investigate the toxic effects of SARS-CoV-2 subunits on human cardiomyocytes.
  • To elucidate the molecular mechanisms of COVID-19-associated cardiac dysfunction and metabolic alterations.

Main Methods:

  • Utilized human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for pseudoviral infection with SARS-CoV-2 subunits.
  • Assessed cellular function, metabolic profiles, mitochondrial activity, and gene expression.
  • Performed transcriptomic analysis to identify dysregulated pathways.

Main Results:

  • Ectopic expression of S and ORF-9B subunits impaired cardiomyocyte contractile function and altered metabolic profiles.
  • Mitochondrial oxidative phosphorylation, membrane potential, and ATP production decreased; reactive oxygen species (ROS) increased with S subunit expression.
  • ORF-9B subunit overexpression led to elevated glycolysis and dysregulated metabolism-related signaling pathways, including HIF-signaling.

Conclusions:

  • SARS-CoV-2 S and ORF-9B subunits induce significant metabolic alterations and cardiac dysfunction in human cardiomyocytes.
  • These findings provide critical insights into the molecular basis of cardiovascular complications in COVID-19 patients.

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