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

The SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) – Angiotensin-converting enzyme 2 (ACE2) interface is the primary molecular gateway for SARS-CoV-2 infection in humans (Yan et al., 2020, Science). The viral spike protein's RBD binds specifically to the extracellular peptidase domain of the host ACE2 receptor, initiating a cascade that leads to viral-host membrane fusion and viral entry (Lan et al., 2020, Nature). This interface is a high-priority therapeutic target because blocking this interaction can effectively neutralize the virus and prevent the onset of COVID-19 (NIH, 2020). Numerous monoclonal antibodies, such as Bamlanivimab and Sotrovimab, have been developed to target the RBD and sterically hinder its binding to ACE2 (FDA, 2021). However, the interface is subject to significant evolutionary pressure, resulting in mutations that can reduce the binding affinity of therapeutic antibodies, a phenomenon known as viral escape (NCBI, 2021). Consequently, ongoing research focuses on identifying conserved epitopes within the interface to develop more resilient, broad-spectrum treatments.

Other names

Spike-ACE2 interfaceSARS-CoV-2 RBD-ACE2 complexS-RBD/ACE2 interfaceSARS-CoV-2 S1-RBD:ACE2 interface

Neutralization of viral entry by blocking the interaction between the viral spike protein and the host ACE2 receptor; competitive inhibition of the receptor-binding domain.