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

The SARS-CoV-2 spike protein receptor-binding domain (RBD) – Angiotensin-converting enzyme 2 (ACE2) protein-protein interaction (PPI) interface is the critical molecular contact point that facilitates the entry of the SARS-CoV-2 virus into human cells [1, 9]. The interaction involves the binding of the viral RBD, a specific region within the S1 subunit of the spike glycoprotein, to the extracellular peptidase domain of the host cell receptor ACE2 [11, 12]. This high-affinity binding event is the first step in the infection process, triggering conformational changes in the spike protein that lead to membrane fusion and the release of the viral genome into the cytoplasm [3, 16]. As the primary gateway for infection, this interface is a major therapeutic target for neutralizing monoclonal antibodies, soluble ACE2 decoys, and small-molecule inhibitors designed to block viral attachment [1, 6, 18]. However, the target is highly dynamic, with the virus continuously evolving mutations in the RBD—such as N501Y, E484K, and L452R—that can enhance binding affinity or enable escape from existing therapeutic agents and immune responses [5, 19, 22].

Other names

SARS-CoV-2 RBD-ACE2 interfaceSpike-ACE2 interaction interfaceRBD-ACE2 complexACE2-interacting surfaceSARS-CoV-2 spike-ACE2 binding site

Inhibition of the protein-protein interaction between the SARS-CoV-2 spike protein receptor-binding domain and the host Angiotensin-converting enzyme 2 (ACE2) receptor, thereby blocking viral attachment and subsequent entry into host cells [1, 3, 11].