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

The interaction between the SARS-CoV-2 spike (S) protein (UniProt P0DTC2) and the human angiotensin-converting enzyme 2 (ACE2) receptor (UniProt Q9BYF1) is the primary mechanism by which the virus gains entry into host cells (PubMed: 32225175). The S protein, specifically its receptor-binding domain (RBD), recognizes and binds to the extracellular peptidase domain of ACE2, triggering a conformational change that facilitates membrane fusion or endocytosis (PubMed: 32142651). This interaction is a critical determinant of viral infectivity and host range, making it a focal point for therapeutic intervention (NIH COVID-19 Treatment Guidelines). Most neutralizing monoclonal antibodies, such as Sotrovimab and Bebtelovimab, function by binding to the RBD and physically blocking the S-ACE2 interface (FDA). However, the rapid evolution of the virus has led to mutations in the spike protein that can reduce the binding affinity of these drugs, presenting a significant challenge for long-term efficacy (PubMed: 35294377). Understanding the structural dynamics of this interaction is essential for developing broad-spectrum antivirals and vaccines that remain effective against emerging variants.

Other names

SARS-CoV-2 S-ACE2 complexSpike-ACE2 binding interfaceSARS-CoV-2 RBD-ACE2 interactionSARS-CoV-2 spike-ACE2 receptor binding

Neutralization of viral particles and inhibition of viral entry by binding to the receptor-binding domain (RBD) of the spike protein, thereby sterically hindering its interaction with the human ACE2 receptor (PubMed: 32511530).