Angiotensin-converting enzyme 2:Spike glycoprotein receptor-binding domain interface (ACE2:Spike RBD interface)

The ACE2:Spike RBD interface is the critical molecular contact site facilitating SARS-CoV-2 entry into human cells. The spike glycoprotein of SARS-CoV-2 contains a receptor-binding domain (RBD) that specifically engages the peptidase domain of the human ACE2 receptor, primarily via a concave surface in the RBD that accommodates the N-terminal helix of ACE2[3][2][5]. Variants in the spike RBD can alter binding affinity and contribute to viral transmissibility and immune escape[4][1]. Disruption of this interface by neutralizing antibodies, soluble ACE2, or small molecules can prevent viral entry and is a major therapeutic strategy for COVID-19[5][4][3]. This molecular interface is extensively characterized structurally (PDB 6M17 and others) and remains a primary target for vaccine, antibody, and antiviral development[3][2][5].

Other names

ACE2–spike interfaceACE2–S protein RBD interfaceACE2–SARS-CoV-2 spike interfaceSARS-CoV-2 spike RBD:ACE2 complex

Blocking spike RBD binding to ACE2 prevents viral entry/fusion[5][3] Neutralization of virus by antibodies that sterically hinder the interface Soluble ACE2 acts as a decoy to sequester spike RBD