Severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain – Angiotensin-converting enzyme 2 interface (SARS-CoV-2 RBD-ACE2 interface)

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) – Angiotensin-converting enzyme 2 (ACE2) interface is the primary molecular gateway for viral entry into human host cells (Source: PubMed 32225176). This protein-protein interaction (PPI) occurs when the RBD of the viral spike (S) glycoprotein binds with high affinity to the peptidase domain of the host's ACE2 receptor, primarily located on the surface of lung, heart, and intestinal cells (Source: UniProt P0DTC2, Q9BYF1). This binding event triggers a series of conformational changes and proteolytic cleavage by host enzymes like TMPRSS2, ultimately leading to viral-host membrane fusion and the release of the viral genome into the cytoplasm (Source: NIH PMC7293463). The interface is characterized by a large contact surface area involving several key residues, such as Gln493 and Asn501 on the RBD, which form hydrogen bonds and salt bridges with residues like Lys31 and Asp38 on ACE2 (Source: Science 367, 1444–1448). Given its critical role in the initial stage of infection, this interface has become a focal point for the development of neutralizing monoclonal antibodies and small-molecule inhibitors designed to block viral attachment (Source: Frontiers in Immunology 11:572525). Therapeutic strategies targeting this interface include not only monoclonal antibodies like bamlanivimab and sotrovimab but also decoy receptors like recombinant soluble ACE2 (Source: Cell 181, 905–913). However, the rapid emergence of viral variants with mutations in the RBD, such as the N501Y and E484K mutations, poses a significant challenge as these changes can enhance binding affinity or facilitate escape from existing therapeutic antibodies (Source: Nature 586, 457–462). Monitoring the evolution of this interface is essential for the ongoing development of next-generation vaccines and pan-coronavirus therapies (Source: Nature Reviews Drug Discovery 20, 697–722).

Other names

RBD-ACE2 interfaceSpike-ACE2 interfaceSARS-CoV-2 S-RBD/ACE2 complexACE2-interacting surfaceACE2IS

Neutralization of viral entry by blocking the protein-protein interaction between the viral spike receptor-binding domain and the host angiotensin-converting enzyme 2 receptor, thereby preventing viral attachment and subsequent membrane fusion.