Severe acute respiratory syndrome coronavirus 2 spike glycoprotein–angiotensin-converting enzyme 2 complex (SARS-CoV-2 Spike–ACE2 complex)

The SARS-CoV-2 spike–ACE2 complex is the molecular assembly formed when the receptor-binding domain (RBD) of the spike glycoprotein from SARS-CoV-2 binds with high affinity to the extracellular domain of human angiotensin-converting enzyme 2 (ACE2) on host cells[1][2][3][4]. This interaction is the critical initial step for viral attachment, membrane fusion, and entry, determining host specificity and enabling SARS-CoV-2 infection in humans[3][4][5]. The spike protein is a class I viral fusion glycoprotein, while ACE2 is an enzyme and membrane-bound receptor. The interface comprises a network of hydrophilic and aromatic interactions, with both protein conformational flexibility and key amino acid contacts contributing to binding specificity and affinity[1][3][5][6]. The complex is the primary target for neutralizing antibodies and vaccine design, as preventing this interaction is an effective therapeutic and prophylactic strategy[4][5]. Major therapeutic approaches focus on blocking or mimicking this binding event, but continual emergence of spike mutations can affect affinity, immune recognition, and drug resistance[6].

Other names

SARS-CoV-2 spike–ACE2 receptor complexspike–ACE2 complexspike glycoprotein–ACE2 complexSARS-CoV-2 S protein–ACE2 complex

Inhibition of spike–ACE2 binding: competitively block or sterically hinder RBD–ACE2 engagement (by antibodies, peptides, small molecules, or soluble ACE2) Conformational interference: stabilize spike in closed conformation or block S2-mediated fusion rearrangements