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

The interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is the fundamental step for viral entry into host cells during COVID-19 infection (Hoffmann et al., 2020, Cell). The spike protein, specifically its receptor-binding domain (RBD), binds with high affinity to the extracellular peptidase domain of ACE2, which is expressed on the surface of various cell types, including lung alveolar epithelial cells (Lan et al., 2020, Nature). This binding event triggers a series of conformational changes and proteolytic cleavage by host enzymes like TMPRSS2, leading to viral-host membrane fusion and the release of the viral genome into the cytoplasm (UniProt P0DTC2). Because this interaction is essential for the viral life cycle, it has become a primary target for neutralizing monoclonal antibodies and decoy receptors designed to block viral attachment (FDA, 2021). However, ACE2 also plays a vital physiological role in the renin-angiotensin system by regulating blood pressure and inflammation through the degradation of angiotensin II (UniProt Q9BYF1). Therefore, therapeutic agents targeting this interaction must be carefully designed to inhibit viral entry without significantly impairing the protective enzymatic activity of ACE2, which could otherwise lead to cardiovascular or pulmonary complications.

Other names

ACE2-Spike interactionSARS-CoV-2 spike-ACE2 complexSpike-ACE2 bindingSARS-CoV-2 entry mechanism

Competitive inhibition of the protein-protein interaction between the viral spike protein receptor-binding domain (RBD) and the host ACE2 receptor, preventing viral attachment and subsequent entry into host cells.