Chemokines simultaneously bind SARS-CoV-2 nucleocapsid protein RNA-binding and dimerization domains

Area of Science:

• Virology
• Immunology
• Structural Biology

Background:

• Viruses produce chemokine-binding proteins to disrupt host chemokine networks, influencing leukocyte migration.
• The SARS-CoV-2 Nucleocapsid (N) protein exhibits high-affinity binding to specific human chemokines (CHK), impairing their chemoattractant capabilities.

Purpose of the Study:

• To investigate the domains of the SARS-CoV-2 Nucleocapsid protein involved in chemokine binding.
• To identify the specific binding site on chemokines targeted by the Nucleocapsid protein.
• To explore therapeutic strategies by blocking the N protein-CHK interaction.

Main Methods:

• Analysis of Nucleocapsid protein domains (RNA-binding and dimerization) for CHK interaction.
• Characterization of chemokine binding sites, including glycosaminoglycan (GAG) and receptor-binding sites.

Main Results:

• Both the RNA-binding and dimerization domains of the SARS-CoV-2 Nucleocapsid protein independently contribute to CHK binding.
• The Nucleocapsid protein interacts with chemokines via the chemokine's GAG-binding site.

Conclusions:

• The SARS-CoV-2 Nucleocapsid protein's interaction with chemokines is mediated by the chemokine's GAG-binding site.
• Targeting this specific interaction presents a potential therapeutic avenue for developing anti-coronavirus drugs.