Angiotensin-converting enzyme 2–SARS-CoV-2 spike protein S1 subunit interaction (ACE2–SARS-CoV-2 S1 interaction)

The interaction between the human Angiotensin-converting enzyme 2 (ACE2) and the SARS-CoV-2 spike protein S1 subunit is the primary gateway for viral entry into host cells (Hoffmann et al., Cell, 2020). ACE2 is a type I transmembrane protein that normally functions as a carboxypeptidase within the renin-angiotensin system, converting Angiotensin II to Angiotensin (1-7) to promote vasodilation and anti-inflammatory effects (UniProt Q9BYF1). During infection, the Receptor Binding Domain (RBD) of the viral S1 subunit binds with high affinity to the extracellular peptidase domain of ACE2, triggering a series of conformational changes that lead to membrane fusion and viral genome release (NCBI, SARS-CoV-2 Spike Protein). This interaction is the focal point for most neutralizing antibody therapies, such as Bamlanivimab and Sotrovimab, which aim to block the RBD from accessing the ACE2 receptor (FDA, COVID-19 Therapeutic EUAs). However, the emergence of viral variants with mutations in the RBD poses a significant challenge, as these changes can reduce the binding affinity of therapeutic antibodies while maintaining or increasing affinity for ACE2 (PubMed, Spike Protein Evolution). Effective therapeutic strategies must balance potent viral neutralization with the preservation of ACE2's endogenous protective functions in the cardiovascular and pulmonary systems.

Other names

ACE2-Spike interactionSARS-CoV-2-ACE2 complexSpike-ACE2 binding interfaceSARS-CoV-2 entry mechanism

Neutralization of viral entry by competitively or sterically inhibiting the binding of the SARS-CoV-2 spike protein S1 subunit to the host cell surface receptor ACE2.