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Engineering Antiviral Agents via Surface Plasmon Resonance
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Calreticulin Regulates SARS-CoV-2 Spike Protein Turnover and Modulates SARS-CoV-2 Infectivity

Nader Rahimi1, Mitchell R White2,3, Razie Amraei1

  • 1Department of Pathology, School of Medicine, Boston University, Boston, MA 02118, USA.

Cells
|December 9, 2023
PubMed

Insights

Calreticulin (CALR) interacts with the SARS-CoV-2 spike protein, influencing its proteostasis and viral infection. This discovery offers new insights into COVID-19 cardiovascular complications.

Area of Science:

  • Molecular Biology
  • Virology
  • Cell Biology

Background:

  • Cardiovascular complications are significant in COVID-19.
  • Mechanisms of SARS-CoV-2 endothelial cell infection are not fully understood.

Purpose of the Study:

  • To investigate the interaction between SARS-CoV-2 spike protein and endothelial cells.
  • To identify host factors involved in SARS-CoV-2 infection and proteostasis.

Main Methods:

  • Biochemical analysis to identify S-RBD interacting proteins.
  • Cell treatments with proteasomal and lysosomal inhibitors.
  • shRNA-mediated knockdown of calreticulin (CALR).

Main Results:

  • Calreticulin (CALR) identified as an S-RBD interacting protein via its proline-rich domain.
  • CALR modulates spike protein proteostasis, particularly in lysosome-dependent degradation.
  • CALR knockdown increased SARS-CoV-2 infection and impaired endothelial cell calcium homeostasis.

Conclusions:

  • CALR plays a crucial role in the ER-lysosome-dependent proteolysis of the SARS-CoV-2 spike protein.
  • CALR's function in spike protein degradation and calcium homeostasis is vital for endothelial cell integrity.
  • Findings suggest a link between CALR, SARS-CoV-2 infection, and COVID-19-associated cardiovascular complications.

Keywords:
COVID-19S-RBDSARS-CoV-2calreticulinendothelial cellsintracellular calcium homeostasisspike protein

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