Molecular dissection of the inter-chain interface of the human Angiotensin-Converting Enzyme 2 (ACE2) receptor with the SARS-CoV-2 Spike-protein

MotivationThe COVID-19 pandemic has prompted many researchers to deepen knowledge of the interactionmechanisms that allow the coronavirus attack to the human target cells. It is well recognized that humanACE2 acts as a cellular receptor of the Spike-protein (Sp) characterizing the virus surface, as for the pastcoronavirus epidemics. The molecular interactions with Sp are of crucial importance for the successfulcoronavirus attack, and their complete understanding can be useful for the definition of the mechanism ofaction as well as for ascertaining possible interaction differences in the case of ACE2 or Sp variants.MethodsWe in silico analyzed the structural features of the chain interface in ACE2/SARS-CoV-2 Sp complexes,described at atomic level by different crystallographic structures available in the RCSB PDB. We observedthe surface interactions by PyMol v1.3, PDBePISA and COCOMAPS, and investigated at visual level themolecular interactions by DiscoveryStudio v20.1.0.ResultsThe results of the structural analysis on the crystallographic complexes of ACE2/SARS-CoV-2 Sp definedwhat amino acid residues interact with the chain-chain interface. Their physiological roles and structuralfeatures were investigated in detail and will be presented together with a comparative analysis thatevidenced differences between the interaction of ACE2 with Sp of SARS-CoV-2 and SARS-CoV (previouslycharacterized), with potential implications on the different health impact of the most recent coronavirus.