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

The SARS-CoV-2 spike protein receptor-binding domain (RBD) – Angiotensin-converting enzyme 2 (ACE2) interface is the primary structural gateway for viral entry into host cells (Lan et al., Nature 2020). The RBD of the viral spike (S) protein binds with high affinity to the extracellular peptidase domain of the human ACE2 receptor, a process that is a prerequisite for membrane fusion and viral infection (Shang et al., Nature 2020). This interface is characterized by a large contact surface area involving multiple residues on both the RBD and the ACE2 alpha-1 helix (UniProt P0DTC2, Q9BYF1). As the critical first step in the viral life cycle, this interaction has been the focus of intensive drug development, resulting in numerous neutralizing monoclonal antibodies such as Bamlanivimab and Sotrovimab (NIH COVID-19 Treatment Guidelines). These therapeutics are designed to bind the RBD and competitively inhibit its association with ACE2, effectively neutralizing the virus's ability to infect cells. However, the interface is subject to rapid evolution, with mutations in variants like Omicron significantly altering binding dynamics and leading to therapeutic escape (Planetary Health, 2022).

Other names

SARS-CoV-2 S-RBD/ACE2 complexSpike-ACE2 interfaceRBD-ACE2 interaction siteSARS-CoV-2 spike-receptor interface

Neutralization of viral particles by blocking the interaction between the viral spike protein and the host cell receptor; competitive inhibition of the receptor-binding domain to prevent attachment and entry.