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. We modeled two RBD-ACE2 complex systems for the two viruses by adding appropriate glycans at 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. Analysis of the S-protein opening pathway reveals that S-protein glycans at N165 and N122 interfere with hydrogen bonds between the receptor-binding domain (RBD) and the N-terminal domain in the up state. We also identified the roles of the S-protein glycans at N165 and N343 in stabilizing the down and up states. Finally, we estimated how epitope exposure for several known antibodies changes along the opening path.

Dynamics and interaction of coronavirus receptor binding domains with glycans

ACS Spring 2022

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