SARS-CoV-2 spike protein – Angiotensin-converting enzyme 2 binding interface (SARS-CoV-2 S-ACE2 interface)

The SARS-CoV-2 spike protein – Angiotensin-converting enzyme 2 (ACE2) binding interface is the critical site of interaction between the virus and the host cell (Lan et al., Nature 2020). The receptor-binding domain (RBD) of the spike protein specifically recognizes and binds to the peptidase domain of ACE2, which serves as the primary entry receptor for the virus in humans (Hoffmann et al., Cell 2020). This interaction triggers a conformational change in the spike protein, facilitating membrane fusion and the release of the viral genome into the cytoplasm (Wrapp et al., Science 2020). Because this interface is essential for infection, it has become a primary target for therapeutic intervention, particularly for neutralizing monoclonal antibodies and vaccines. Drugs targeting this interface aim to block the physical contact between the RBD and ACE2, thereby preventing the virus from colonizing host tissues (Starr et al., Science 2021). However, the high mutation rate of the spike protein, especially within the RBD, poses a significant challenge as it can lead to the emergence of variants that evade existing treatments (Cameroni et al., Nature 2022).

Other names

SARS-CoV-2 S-ACE2 PPISpike-ACE2 interfaceRBD-ACE2 binding siteSARS-CoV-2 receptor binding domain-ACE2 interface

Neutralizing agents, primarily monoclonal antibodies, bind to specific epitopes on the SARS-CoV-2 spike protein's receptor-binding domain (RBD) that overlap with the ACE2 binding site. This binding sterically blocks the interaction between the virus and the host receptor, preventing viral attachment and subsequent entry (Taylor et al., Nature Reviews Genetics 2021).