SARS-CoV-2 spike glycoprotein receptor-binding domain–ACE2 interface

The **SARS-CoV-2 spike glycoprotein receptor-binding domain–ACE2 interface** is the critical molecular contact between the virus and human host cells that initiates COVID-19 infection. The spike protein on the viral surface contains an RBD (receptor-binding domain) that specifically binds to the extracellular N-terminal domain of the angiotensin-converting enzyme 2 (ACE2) receptor on human cells, predominantly respiratory and intestinal epithelia[1][3][4]. This interaction is highly specific, involving networks of hydrophilic, electrostatic, and hydrophobic contacts between key residues: in the RBD (notably Q493, N501, K417, F486, and others) and in ACE2 (notably K31, E35, D38, Y41, K353, Y83, among others)[4][5][6]. Viral entry inhibitors target this interface to prevent the spike from engaging and fusing with the host cell membrane, blocking infection. Variants of concern often harbor mutations at the RBD–ACE2 interface that can increase binding affinity or confer resistance to antibody therapies[1][4][6]. This protein–protein interaction is a principal therapeutic target for neutralizing antibodies, peptide inhibitors, and small molecules, and is central to vaccine and antiviral drug development efforts for COVID-19[1][2][5].

Other names

SARS-CoV-2 spike RBD–ACE2 interfaceSARS-CoV-2 Spike–ACE2 binding siteSpike glycoprotein RBD–ACE2 protein-protein interfaceS protein RBD–ACE2 interaction

Inhibition of spike RBD–ACE2 binding to prevent viral entry Neutralization of virus by competitive binding to RBD Preventing conformational change required for membrane fusion