Heparan Sulfate Proteoglycans as Attachment Factor for SARS-CoV-2

Area of Science:

• Virology
• Glycobiology
• Drug Discovery

Background:

• The global pandemic caused by SARS-CoV-2 necessitates urgent development of therapeutic strategies.
• Understanding the initial steps of viral entry is crucial for designing effective treatments.

Purpose of the Study:

• To investigate the interaction between SARS-CoV-2 spike protein and heparan sulfate (HS).
• To identify potential therapeutic targets based on HS-RBD interactions.

Main Methods:

• Utilized microarray binding experiments with a heparan sulfate oligosaccharide library.
• Employed surface plasmon resonance to determine binding affinities.
• Assessed the effect of heparin and HS oligosaccharides on viral binding to cells and tissues.

Main Results:

• SARS-CoV-2 receptor binding domain (RBD) binds HS in a length- and sequence-dependent manner, with a minimal binding epitope identified.
• Heparin exhibits higher affinity for the SARS-CoV-2 spike protein than RBD alone.
• Exogenous heparin or HS oligosaccharides inhibited RBD binding to cells, and HS removal reduced binding to tissues.

Conclusions:

• Heparan sulfate acts as an initial attachment site, facilitating SARS-CoV-2 interaction with host cells.
• HS oligosaccharides demonstrate potential as therapeutic agents by blocking viral cell entry.
• Simultaneous binding of ACE2 and HS to RBD suggests a model for viral attachment and entry.