Distinct Differences in the Interactions of Receptor Binding Domains of SARS-CoV-2 and SARS-CoV with Human ACE2

Abstract

Coronaviruses have created multiple infectious diseases in the last two decades with dreadful 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 (hACE2) using the spike glycoprotein. While ACE2 acts as a 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-hACE2 complex systems for the two viruses by adding appropriate glycans at the N- and O-glycosylation sites as suggested by mass spectroscopy experiments.