A sialic acid binding site in a human picornavirus

Area of Science:

• Virology
• Structural Biology
• Glycobiology

Background:

• Picornaviruses, including coxsackievirus A24 variant (CVA24v) and enterovirus 70 (EV70), cause outbreaks of acute hemorrhagic conjunctivitis (AHC).
• No vaccines or antiviral drugs are currently available for AHC, which can lead to serious complications like neurological impairments.
• Both viruses utilize 5-N-acetylneuraminic acid (Neu5Ac) for cell attachment, suggesting a link between glycan receptor specificity and disease pathology.

Purpose of the Study:

• To elucidate the structural basis of picornavirus-glycan interactions.
• To identify specific glycan binding preferences of CVA24v.
• To provide a foundation for designing novel antiviral interventions against AHC.

Main Methods:

• Determined the high-resolution crystal structure of CVA24v in complex with Neu5Ac-terminating glycans.
• Screened various Neu5Ac-bearing glycans for binding affinity to CVA24v.
• Performed biochemical assays and molecular dynamics simulations to analyze binding interactions.

Main Results:

• The study reports the structure of CVA24v bound to Neu5Ac-containing glycans at 1.40 Å resolution.
• CVA24v demonstrated a binding preference for α2,6-linked sialic acid glycans over other linkages.
• Molecular dynamics simulations supported these findings, indicating enhanced viral capsid contacts with α2,6-linked glycans.

Conclusions:

• The structural and biochemical data reveal specific glycan receptor interactions for CVA24v.
• The identified preference for α2,6-linked sialic acid glycans offers a target for antiviral drug design.
• These findings pave the way for developing new strategies to prevent and treat AHC.