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

The SARS-CoV-2 spike protein – Angiotensin-converting enzyme 2 (ACE2) interface is the critical molecular contact point that mediates the entry of the SARS-CoV-2 virus into human host cells (Hoffmann et al., 2020, Cell). This interface involves the binding of the viral receptor-binding domain (RBD), located within the S1 subunit of the spike glycoprotein, to the extracellular peptidase domain of the host cell surface protein ACE2 (Lan et al., 2020, Nature). This high-affinity interaction is the prerequisite for subsequent proteolytic cleavage of the spike protein and membrane fusion, which allows the viral RNA to enter the cytoplasm (Wrapp et al., 2020, Science). As the primary determinant of viral infectivity and host range, this interface is the leading target for therapeutic development, including vaccines and monoclonal antibodies (Harvey et al., 2021, Nature Reviews Microbiology). Most neutralizing antibodies function by binding to the RBD and sterically hindering its association with ACE2, effectively blocking the virus from entering the cell (Taylor et al., 2021, Nature Reviews Immunology). However, the interface is subject to significant evolutionary pressure, leading to the emergence of variants of concern with mutations that enhance binding affinity or evade existing immune responses (Planans et al., 2021, Nature). Therapeutic strategies also include the use of decoy ACE2 receptors and small molecule inhibitors designed to disrupt this specific protein-protein interaction (Chan et al., 2020, Science). Understanding the structural dynamics of this interface is essential for predicting the impact of new mutations and developing pan-coronavirus therapies.

Other names

SARS-CoV-2 S-ACE2 complexSpike-ACE2 interactionRBD-ACE2 interfaceSARS-CoV-2 receptor binding domain-ACE2 interfaceSARS-CoV-2 S-ACE2 PPI

Neutralization of the virus by blocking the receptor-binding domain (RBD) of the spike protein from interacting with the host Angiotensin-converting enzyme 2 (ACE2) receptor, thereby preventing viral entry into the cell.