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

The SARS-CoV-2 spike receptor-binding domain (RBD)–Angiotensin-converting enzyme 2 (ACE2) interface is the critical molecular contact point that facilitates the entry of the SARS-CoV-2 virus into human cells (Lan et al., 2020, Nature). The viral spike protein uses its RBD to bind with high affinity to the extracellular peptidase domain of ACE2, which is expressed on the surface of various host cells, including those in the lungs, heart, and kidneys (Hoffmann et al., 2020, Cell). 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 (Wrapp et al., 2020, Science). Because this interaction is essential for infection, the interface has become a primary target for therapeutic intervention (Ju et al., 2020, Nature). Most neutralizing monoclonal antibodies and vaccine-induced antibodies work by binding to the RBD and sterically hindering its interaction with ACE2 (Hansen et al., 2020, Science). However, the rapid evolution of the virus has led to mutations within this interface, such as those seen in the Omicron variant, which can reduce the binding affinity of certain drugs and necessitate the development of broader-spectrum inhibitors (Cao et al., 2022, Nature).

Other names

SARS-CoV-2 S-RBD–ACE2 complexSpike-ACE2 interfaceSARS-CoV-2 RBD:ACE2 interaction site

Competitive inhibition of the protein-protein interaction between the viral spike protein receptor-binding domain and the host cell angiotensin-converting enzyme 2 receptor, thereby preventing viral attachment and entry (Hansen et al., 2020, Science; Ju et al., 2020, Nature).