Angiotensin-converting enzyme 2–SARS-CoV-2 spike receptor-binding domain interaction (ACE2–SARS-CoV-2 RBD interaction)

The interaction between the human Angiotensin-converting enzyme 2 (ACE2) and the SARS-CoV-2 spike protein's receptor-binding domain (RBD) is the primary mechanism by which the virus attaches to and enters host cells. ACE2 is a cell-surface enzyme that plays a vital physiological role in the renin-angiotensin system by converting the vasoconstrictor angiotensin II into the vasodilator angiotensin (1-7). SARS-CoV-2 exploits this receptor, using its spike protein to mimic natural ligands and gain entry into the respiratory epithelium and other tissues. Because this interaction is essential for viral infectivity, it is a major target for therapeutic strategies, including neutralizing monoclonal antibodies that bind the RBD and soluble ACE2 decoys that sequester the virus. A significant challenge in targeting this interaction is the high rate of viral mutation, which can alter the RBD structure and allow the virus to evade immune recognition or drug binding. Understanding the structural dynamics of this interface is crucial for the development of broad-spectrum antivirals and effective vaccines.

Other names

ACE2-Spike interactionSARS-CoV-2 RBD-ACE2 complexSpike-ACE2 interfaceSARS-CoV-2-host cell attachment

Inhibition of viral entry by competitively blocking the binding interface between the SARS-CoV-2 spike protein receptor-binding domain and the human ACE2 receptor.