The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor

• Published in: Viruses 2020-04, Vol.12 (5), p.497
• Main Authors: Brielle, Esther S, Schneidman-Duhovny, Dina, Linial, Michal
• Format: Article
• Language: English
• Subjects: ACE2; Angiotensin-Converting Enzyme 2; Atoms & subatomic particles; Betacoronavirus - chemistry; Betacoronavirus - metabolism; Binding sites; Coronaviridae; coronavirus evolution; Coronavirus NL63, Human - chemistry; Coronavirus NL63, Human - metabolism; Coronaviruses; COVID-19; Disease transmission; Epidemics; Exploration; Humans; Interfaces; Middle East respiratory syndrome; molecular dynamics; Molecular Dynamics Simulation; Peptidyl-Dipeptidase A - chemistry; Peptidyl-Dipeptidase A - metabolism; Protein Domains; Proteins; protein–protein complex; Receptors, Virus; Respiratory diseases; SARS Virus - chemistry; SARS Virus - metabolism; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Simulation; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; Viruses; virus–host interactions
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v12050497

The COVID-19 disease has plagued over 200 countries with over three million cases and has resulted in over 200,000 deaths within 3 months. To gain insight into the high infection rate of the SARS-CoV-2 virus, we compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts. SARS-CoV and SARS-CoV-2 have comparable binding affinities achieved by balancing energetics and dynamics. The SARS-CoV-2-ACE2 complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to the SARS-CoV-ACE2 complex. These findings expose an exceptional evolutionary exploration exerted by coronaviruses toward host recognition. We postulate that the versatility of cell receptor binding strategies has immediate implications for therapeutic strategies.