SARS-CoV-2 spike protein receptor-binding domain (RBD) – Angiotensin-converting enzyme 2 (ACE2) 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 critical site of interaction that facilitates viral entry into human host cells (Lan et al., Nature 2020). The RBD of the viral spike (S) protein specifically recognizes and binds to the peptidase domain of ACE2, which is expressed on the surface of various tissues, including the lungs, heart, and kidneys (UniProt P0DTC2, Q9BYF1). This binding event triggers a conformational change in the spike protein, leading to membrane fusion and the release of the viral genome into the cytoplasm (PubMed: 32225175). Because this interface is essential for infection, it has become a primary target for therapeutic intervention, particularly for neutralizing monoclonal antibodies and vaccines (NIH COVID-19 Treatment Guidelines). Drugs targeting this region, such as Bamlanivimab and Sotrovimab, aim to sterically hinder the RBD-ACE2 interaction, thereby preventing the virus from attaching to and infecting host cells (FDA Fact Sheets). However, the rapid evolution of the virus has led to mutations within the RBD that can reduce the binding affinity of certain therapeutics, presenting a significant challenge for long-term efficacy (CDC: SARS-CoV-2 Variant Classifications).

Other names

SARS-CoV-2 RBD-ACE2 complexSpike-ACE2 interfaceRBD-ACE2 binding siteSARS-CoV-2 S-RBD:hACE2 interfaceSARS-CoV-2 spike protein receptor-binding domain – Angiotensin-converting enzyme 2 interface

Neutralization of viral entry by competitively or sterically blocking the interaction between the SARS-CoV-2 spike protein receptor-binding domain (RBD) and the host cell receptor angiotensin-converting enzyme 2 (ACE2) (PubMed: 32225175, NIH COVID-19 Treatment Guidelines).