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Host and viral proteins involved in SARS-CoV-2 infection differentially bind heme

Marie-T Hopp1, Dhruv C Rathod1, Diana Imhof1

  • 1Pharmaceutical Biochemistry and Bioanalytics, Pharmaceutical Institute, University of Bonn, Bonn, Germany.

Protein Science : a Publication of the Protein Society
|September 26, 2022
PubMed

Insights

Severe COVID-19 can cause autoimmune reactions and hemolysis. This study shows heme from red blood cells binds to SARS-CoV-2 proteins, potentially worsening the disease and highlighting the need to consider heme in COVID-19 patients.

Area of Science:

  • Biochemistry
  • Virology
  • Immunology

Background:

  • SARS-CoV-2 infection can trigger autoimmune hemolytic complications.
  • Heme released during hemolysis promotes inflammation and coagulation, potentially worsening COVID-19.
  • The SARS-CoV-2 accessory protein 7a is implicated in inducing proinflammatory signals.

Purpose of the Study:

  • To experimentally investigate heme binding to key SARS-CoV-2 viral proteins (spike glycoprotein, protein 7a) and the host protein ACE2.
  • To analyze the binding characteristics and affinities of heme to these proteins.
  • To confirm the relevance of heme-binding motifs in the context of COVID-19 pathogenesis.

Main Methods:

  • Chemical synthesis of SARS-CoV-2 protein 7a, including analysis of disulfide-bonded isomers.
  • Surface plasmon resonance spectroscopy to assess binding kinetics and affinities.
  • In silico studies to complement experimental findings.

Main Results:

  • Experimental evidence confirms heme binding to SARS-CoV-2 spike glycoprotein, protein 7a, and ACE2.
  • A transient, biphasic binding behavior was observed for heme.
  • Heme-binding affinities were determined to be in the nano- to low micromolar range.

Conclusions:

  • The findings confirm previously suggested heme-binding motifs on SARS-CoV-2 proteins.
  • Labile heme should be considered in patients with pre-existing or SARS-CoV-2-induced hemolytic conditions.
  • Understanding heme-protein interactions may offer new insights into COVID-19 severity and treatment.

Keywords:
ACE2COVID-19SARS-CoV-2hemehemolysisprotein 7aspike glycoprotein

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