Coronaviruses have been responsible for multiple infectious diseases in the last two decades with significant global impact, including most recently COVID-19 caused by the SARS-CoV-2 virus. The SARS-CoV-2 virus binds to the human angiotensin-converting enzyme (ACE2) using the spike glycoprotein. While ACE2 is the receptor for both SARS-CoV-2 and SARS-CoV, it binds much more strongly (~4 times) to the spike glycoprotein of SARS-CoV-2. To investigate this difference in binding affinity, we modeled two RBD-ACE2 complex systems for the two viruses by adding appropriate glycans at the N- and O-glycosylation sites as suggested by mass spectroscopy experiments. We performed multiple two-microsecond molecular dynamics simulations of the RBD-ACE2 complex for both coronaviruses. We report distinct differences between the interactions of human ACE2 glycans with SARS-CoV-2 and those with SARS-CoV. The interaction site of N322 on SARS-CoV is blocked by the presence of the N357 glycan of SARS-CoV. The absence of this glycosylation site on SARS-CoV-2 may enhance the binding between the receptor-binding domain of the virus and ACE2. Our analysis demonstrates that the glycan shielding in this complex behaves differently between SARS-CoV-2 and SARS-CoV. Additionally, we show that each of the glycans has a specific interaction pattern that is unique to each virus.

Differences in the interactions of receptor binding domains of SARS-CoV-2 and SARS-CoV with ACE2 glycans

ACS Fall 2021

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