Angiotensin-converting enzyme 2 – SARS-CoV-2 spike protein interface (ACE2–SARS-CoV-2 S protein interface)

The **angiotensin-converting enzyme 2 – SARS-CoV-2 spike protein interface** represents the critical molecular contact site whereby the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein attaches to the human ACE2 receptor, facilitating viral entry into host cells[2][3][4]. This interaction is mediated primarily through a set of conserved amino acid residues in the spike RBD (notably within residues 438–506) engaging the N-terminal peptidase domain of ACE2, leading to viral attachment, conformational rearrangement of the spike, and subsequent membrane fusion required for infection[2][3][7]. Disrupting this interface is a validated antiviral strategy, forming the mechanistic basis for therapeutic agents such as neutralizing antibodies, soluble ACE2 constructs, and designed peptides or miniproteins. The ACE2–spike RBD interface is a focus of vaccine and drug development against COVID-19, but interventions must account for the physiological importance of ACE2 and the potential for viral resistance through spike mutations[3][4][6].

Other names

ACE2–Spike protein interfaceACE2–S protein interfaceACE2–RBD interface

Competitive inhibition of spike-ACE2 binding (prevents viral attachment and fusion)[2][4] Neutralization of spike protein via monoclonal antibodies (blocks ACE2 binding site) Allosteric modulation of ACE2 or spike RBD conformation to prevent productive interaction[1] Decoy receptor strategy (soluble ACE2 binds spike and blocks virus from binding to cell-surface ACE2)[4]