SARS-CoV-2 spike protein receptor-binding domain–Angiotensin-converting enzyme 2 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 molecular contact site that mediates the entry of the SARS-CoV-2 virus into human host cells. The RBD, located within the S1 subunit of the viral spike protein, specifically recognizes and binds to the extracellular peptidase domain of the host cell surface protein ACE2 (UniProt P0DTC2, P17858). This binding event is the initial and essential step of the infection process, triggering conformational changes that lead to membrane fusion and viral genome delivery (Lan et al., 2020, Nature). Because of its indispensable role in viral pathogenesis, this interface is the primary target for neutralizing antibodies, both those induced by vaccines and those developed as monoclonal antibody therapies like Bebtelovimab and Sotrovimab (NIH, 2022). These therapeutics typically function by sterically hindering the RBD-ACE2 interaction, effectively preventing the virus from attaching to and infecting susceptible cells. However, the interface is highly susceptible to mutations, such as those seen in the Omicron variant, which can alter binding affinity and facilitate immune evasion, presenting a continuous challenge for drug development and public health.

Other names

SARS-CoV-2 spike-ACE2 interfaceRBD–ACE2 complexSARS-CoV-2 S-RBD/hACE2 interfaceSpike protein receptor-binding domain–Angiotensin-converting enzyme 2 interface

Inhibition of viral attachment and entry by blocking the physical interaction between the SARS-CoV-2 spike protein receptor-binding domain (RBD) and the human Angiotensin-converting enzyme 2 (ACE2) receptor.