Angiotensin-converting enzyme 2–Spike glycoprotein complex (ACE2–Spike complex)

The angiotensin-converting enzyme 2–spike glycoprotein interaction refers to the direct binding of the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein to the N-terminal helix of the host cell surface protein ACE2. This interaction facilitates viral attachment to and entry into human cells, triggering membrane fusion and subsequent infection. The binding interface is characterized by a network of hydrogen bonds, salt bridges, and hydrophobic contacts, primarily involving 20 residues on ACE2 and 17 residues on the viral spike RBD[1][2][3][5]. Enhanced binding affinity due to mutations in the spike RBD is a major driver of increased infectivity and variant emergence. Therapeutic strategies aim to inhibit this interaction, typically by targeting one or both binding partners to prevent viral entry without impairing the essential enzymatic functions of ACE2[4]. The complex is of paramount importance in understanding and developing therapeutics for COVID-19 and related coronavirus infections.

Other names

ACE2–Spike interactionACE2–SARS-CoV-2 Spike bindingACE2–S protein interactionS protein–ACE2 bindingSARS-CoV-2 receptor binding interface

Competitive inhibition of Spike RBD–ACE2 binding (neutralizing by blocking attachment) - Allosteric modulation reducing binding affinity - Steric hindrance by antibody binding - Decoy receptor (soluble ACE2 sequesters Spike)