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

The interaction between the SARS-CoV-2 spike (S) protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is the critical first step in the infection process of COVID-19 (Hoffmann et al., 2020). The viral S protein consists of two subunits, S1 and S2; the S1 subunit contains the receptor-binding domain (RBD) that specifically targets the peptidase domain of ACE2 on the surface of host cells, particularly in the respiratory epithelium (Yan et al., 2020). Upon binding, the S protein undergoes proteolytic cleavage and structural rearrangement, which mediates the fusion of the viral and host cell membranes (UniProt P0DTC2). This interaction is the primary target for most neutralizing monoclonal antibodies and the basis for current vaccine designs, which aim to elicit antibodies that block this binding site (NIH, 2021). Therapeutic strategies focusing on this interaction are highly effective but face significant challenges due to the high mutation rate of the S protein, leading to variants that can bypass existing treatments (FDA, 2022).

Other names

SARS-CoV-2 S-ACE2 bindingSpike-ACE2 complexSARS-CoV-2 entry mechanismS-protein:ACE2 interactionSARS-CoV-2 S-ACE2 interaction

Neutralization of viral entry by competitively inhibiting the binding of the viral spike protein receptor-binding domain (RBD) to the host cell angiotensin-converting enzyme 2 (ACE2) receptor (Hoffmann et al., 2020; Yan et al., 2020).