Angiotensin-converting enzyme 2–SARS-CoV-2 spike protein receptor-binding domain interaction (ACE2–SARS-CoV-2 spike RBD interaction)

The interaction between the human Angiotensin-converting enzyme 2 (ACE2) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is the critical initial step for viral infection (Hoffmann et al., 2020, Cell). 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 the infection process, the RBD of the viral S1 subunit binds with high affinity to the extracellular peptidase domain of ACE2, which triggers a conformational change in the spike protein that facilitates membrane fusion (Lan et al., 2020, Nature). This interaction has been the primary target for therapeutic development, leading to the creation of neutralizing monoclonal antibodies and decoy receptors like soluble ACE2 (Alunacedase alfa) that competitively block the binding site (FDA, 2021; ClinicalTrials.gov NCT04335136). However, the rapid evolution of the SARS-CoV-2 virus has resulted in numerous mutations within the RBD, such as those found in the Omicron variant, which can significantly alter binding affinity and lead to resistance against existing antibody therapies (Harvey et al., 2021, Nature Reviews Microbiology). Understanding the structural and biochemical nuances of this interaction remains essential for developing broad-spectrum antivirals and vaccines that can withstand viral diversification.

Other names

ACE2-Spike interactionSARS-CoV-2-ACE2 complexSpike-ACE2 interfaceSARS-CoV-2 entry receptor interaction

Competitive inhibition of the protein-protein interaction between the viral spike protein receptor-binding domain and the host ACE2 receptor to prevent viral attachment and entry.