SARS-CoV-2 nucleocapsid protein forms complexes with soluble complement regulatory proteins that can bind to the...

Area of Science:

• Immunology
• Virology
• Biochemistry

Background:

• SARS-CoV-2 nucleocapsid protein is found in COVID-19 patient plasma and correlates with disease severity.
• Nucleocapsid protein is an immunomodulatory agent, inducing pro-inflammatory cytokine release.
• COVID-19 is associated with complement system dysregulation.

Purpose of the Study:

• To investigate potential interactions between SARS-CoV-2 proteins (nucleocapsid and spike) and complement regulatory proteins (CRPs).
• To determine if SARS-CoV-2 proteins modulate the complement system.

Main Methods:

• Binding assays were performed to test interactions between nucleocapsid protein, spike protein, and various CRPs (C1-inhibitor, C4-binding protein, factor H, vitronectin).
• Interactions with recombinant spike protein and SARS-CoV-2 virions were assessed.
• Formation of a virion-nucleocapsid-CRP complex was investigated.

Main Results:

• Nucleocapsid protein, but not spike protein, binds to multiple CRPs, including C1-inhibitor, C4-binding protein, factor H, and vitronectin.
• Nucleocapsid protein binds to both recombinant spike protein and SARS-CoV-2 virions.
• A complex involving virions, nucleocapsid protein, and CRPs can be formed.

Conclusions:

• SARS-CoV-2 nucleocapsid protein interacts with key complement regulatory proteins.
• This interaction, mediated by the nucleocapsid protein, may contribute to complement system dysregulation in COVID-19.
• Further research is needed to elucidate the complement modulation strategies employed by SARS-CoV-2 via its nucleocapsid protein.