SARS-CoV-2 spike protein–angiotensin-converting enzyme 2 receptor interface (Spike–ACE2 interface)

The SARS-CoV-2 spike protein–angiotensin-converting enzyme 2 (ACE2) receptor interface is the molecular interaction site at which the viral spike glycoprotein binds to the host ACE2 receptor, mediating viral attachment and entry into host cells[2][6][8]. The spike protein's receptor-binding domain (RBD) specifically recognizes and binds to the extracellular peptidase domain of ACE2. This interaction triggers conformational changes in the spike protein, activates host protease cleavage at the S1/S2 boundary, and facilitates the fusion of viral and cellular membranes[6]. Disrupting the spike–ACE2 interface is a primary therapeutic strategy for preventing infection, targeted by neutralizing antibodies, peptide inhibitors, and decoy receptors[2][4]. The site is highly adaptable, with viral mutations frequently evolving to optimize binding or escape immune blockade, posing challenges for drug and vaccine design[8][2]. While not a classical receptor or enzyme, the spike–ACE2 interface defines a critical gateway for viral pathogenesis and is central to both acute and chronic COVID-19 disease processes.

Other names

Spike–ACE2 interfaceSARS-CoV-2 spike–ACE2 binding siteSpike glycoprotein–ACE2 interactionSARS-CoV-2 S protein–ACE2 interfaceViral spike–ACE2 complex

Blockade of spike–ACE2 interaction, preventing viral attachment and membrane fusion; Allosteric inhibition by stabilizing ACE2 or the spike in non-binding conformations; Competitive inhibition via decoy ligands (soluble ACE2)