Severe acute respiratory syndrome coronavirus 2 Spike protein:Angiotensin-converting enzyme 2 interaction (SARS-CoV-2 S:ACE2) (SARS-CoV-2 S:ACE2)

The interaction between the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike (S) protein and the human Angiotensin-converting enzyme 2 (ACE2) receptor is the fundamental mechanism for viral attachment and entry into host cells [2, 10]. The Spike protein is a trimeric class I fusion glycoprotein consisting of S1 and S2 subunits; the S1 subunit contains the receptor-binding domain (RBD) that specifically recognizes the extracellular peptidase domain of ACE2 [4, 11]. Upon binding, the Spike protein undergoes significant conformational rearrangements that facilitate membrane fusion and the release of the viral genome into the cytoplasm [10, 11]. This protein-protein interaction is a primary target for therapeutic intervention, particularly for neutralizing monoclonal antibodies designed to block the RBD-ACE2 interface [3, 6]. However, the emergence of viral variants with mutations in the RBD, such as N501Y and E484K, has increased binding affinity and enabled immune evasion, necessitating the continuous development of broad-spectrum inhibitors and updated biologics [12, 14]. Furthermore, the binding of the Spike protein may interfere with the physiological enzymatic activity of ACE2, potentially contributing to the dysregulation of the renin-angiotensin system and exacerbating COVID-19 pathogenesis [7].

Other names

Spike-ACE2 interactionS-ACE2 complexSARS-CoV-2 S protein binding to ACE2SARS-CoV-2 RBD:ACE2 interactionCoronavirus spike-receptor interactionSARS-CoV-2 S-ACE2 interface

Neutralization of viral entry by competitively inhibiting the binding of the SARS-CoV-2 Spike protein receptor-binding domain (RBD) to the host cell Angiotensin-converting enzyme 2 (ACE2) receptor, thereby preventing viral attachment and subsequent membrane fusion [2, 6, 15].