ACE2 glycans preferentially interact with SARS-CoV-2 over SARS-CoV

Area of Science:

• Virology
• Structural Biology
• Glycobiology

Background:

• The severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 utilize the angiotensin-converting enzyme 2 (ACE2) receptor for host cell entry.
• Glycosylation of both the viral spike protein and the host ACE2 receptor plays a critical role in viral-host interactions.

Purpose of the Study:

• To investigate the distinct interactions of ACE2 glycans with the receptor-binding domains (RBDs) of SARS-CoV-2 and SARS-CoV.
• To elucidate how specific glycosylation sites on ACE2 influence binding affinity and potentially viral infectivity.

Main Methods:

• Comparative analysis of glycan interactions with viral RBDs.
• Structural and biochemical studies of ACE2-RBD complexes.

Main Results:

• ACE2 glycan at N322 enhances interaction with SARS-CoV-2 RBD.
• ACE2 glycan at N90 may provide protection against both SARS-CoV and SARS-CoV-2.
• SARS-CoV RBD glycan at N357 blocks interaction with ACE2 glycan at N322.
• Absence of N357 glycosylation on SARS-CoV-2 RBD may enhance ACE2 binding.

Conclusions:

• ACE2 glycosylation patterns differentially modulate interactions with SARS-CoV and SARS-CoV-2 RBDs.
• Specific glycan modifications on ACE2 and viral RBDs are key determinants of viral tropism and infectivity.