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

The interaction between the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain (RBD) and the human host cell receptor Angiotensin-converting enzyme 2 (ACE2) is the critical initial step for viral infection (Lan et al., Nature 2020). The RBD, a key component of the S1 subunit of the viral spike protein, recognizes and binds to the extracellular domain of ACE2 with high affinity, facilitating viral attachment to the host cell membrane (UniProt P0DTC2, Q9BYF1). This binding event is followed by proteolytic processing of the spike protein, which triggers membrane fusion and the delivery of the viral RNA into the host cell (NIH, 2021). As the primary mediator of viral entry, this protein-protein interaction is a major focus for therapeutic intervention, particularly for neutralizing monoclonal antibodies like Bamlanivimab and Casirivimab (FDA, 2020). These therapeutics work by binding to the RBD and physically blocking its access to ACE2, thereby preventing the virus from infecting cells. However, the emergence of viral variants with mutations in the RBD poses a significant challenge, as these changes can reduce the binding affinity of existing drugs and lead to immune escape (CDC, 2022).

Other names

SARS-CoV-2 S-RBD/ACE2 complexSpike-ACE2 interfaceSARS-CoV-2 RBD-hACE2 interactionSARS-CoV-2 Spike-ACE2 PPI

Neutralizing monoclonal antibodies bind to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, sterically blocking its interaction with the host cell receptor Angiotensin-converting enzyme 2 (ACE2) and preventing viral entry (FDA, 2020; Lan et al., Nature 2020).