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

The interaction between human Angiotensin-converting enzyme 2 (ACE2) and the SARS-CoV-2 spike (S) protein is the primary mechanism for viral entry into host cells (Hoffmann et al., 2020, Cell). ACE2 is a type I transmembrane protein that physiologically regulates the renin-angiotensin system by converting angiotensin II to angiotensin (1-7), providing cardioprotective and anti-inflammatory effects (UniProt Q9BYF1). The SARS-CoV-2 virus utilizes the receptor-binding domain (RBD) of its S1 subunit to bind the extracellular peptidase domain of ACE2 with high affinity (Lan et al., 2020, Nature). This binding event triggers conformational changes and subsequent membrane fusion, facilitated by host proteases like TMPRSS2 (NIH, 2021). Therapeutic interventions, such as monoclonal antibodies (e.g., Sotrovimab) and decoy receptors, aim to disrupt this protein-protein interaction to prevent infection (FDA, 2022). However, the rapid evolution of the spike protein leads to variants of concern that can evade these therapies by altering the binding interface (CDC, 2023).

Other names

ACE2-Spike protein interactionSARS-CoV-2 receptor bindingACE2-RBD complexSARS-CoV-2 entry mechanism

Neutralizing monoclonal antibodies bind to specific epitopes on the SARS-CoV-2 spike protein's receptor-binding domain (RBD), sterically hindering its ability to interact with the host ACE2 receptor and thereby blocking viral attachment and entry (Taylor et al., 2021, Nature Reviews Genetics).