Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors

Area of Science:

• Virology
• Structural Biology
• Infectious Diseases

Background:

• Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness with no available vaccines or treatments.
• MERS-CoV infection initiates through the spike (S) glycoprotein binding to sialosides and dipeptidyl-peptidase 4 receptors.

Purpose of the Study:

• To elucidate the structural basis of MERS-CoV S glycoprotein engagement with sialylated receptors.
• To understand the specificity of MERS-CoV S for different sialoside structures.

Main Methods:

• Determined cryo-electron microscopy (cryo-EM) structures of the MERS-CoV S protein in complex with various sialosides.
• Analyzed the structural interactions between MERS-CoV S and sialylated receptors at 2.7-3.0 Å resolution.

Main Results:

• Identified a conserved groove on the MERS-CoV S protein essential for sialoside binding and viral entry into human airway epithelial cells.
• Demonstrated that MERS-CoV S exhibits selectivity for α2,3-linked sialosides over α2,6-linked sialosides due to enhanced interactions.
• Provided high-resolution structures of MERS-CoV S complexed with 5-N-acetyl neuraminic acid, 5-N-glycolyl neuraminic acid, sialyl-LewisX, α2,3-sialyl-N-acetyl-lactosamine, and α2,6-sialyl-N-acetyl-lactosamine.

Conclusions:

• The study provides a structural framework explaining MERS-CoV attachment to sialoside receptors.
• The identified conserved groove represents a potential vulnerability for developing inhibitors of viral entry.
• Understanding MERS-CoV S sialoside specificity is key for designing effective antiviral strategies.