SARS-CoV-2 spike protein receptor-binding domain – Angiotensin-converting enzyme 2 interaction interface (SARS-CoV-2 RBD-ACE2 interface)

The SARS-CoV-2 spike protein receptor-binding domain (RBD) – Angiotensin-converting enzyme 2 (ACE2) interaction interface is the primary molecular gateway for viral entry into human cells. The RBD, a key component of the S1 subunit of the SARS-CoV-2 spike protein, specifically recognizes and binds to the extracellular peptidase domain of the host receptor ACE2 (Lan et al., 2020, Nature). This high-affinity protein-protein interaction (PPI) is the prerequisite for subsequent proteolytic cleavage of the spike protein and fusion of the viral and host cell membranes (Hoffmann et al., 2020, Cell). Given its essential role in the viral life cycle, this interface is a major target for therapeutic intervention, particularly for neutralizing monoclonal antibodies like Bamlanivimab and Casirivimab, which competitively inhibit RBD binding to ACE2 (FDA, 2021). Clinical efficacy of these drugs is directly linked to their ability to block this interface, thereby preventing infection of susceptible cells. However, the interface is subject to significant evolutionary pressure, leading to mutations in the RBD that can enhance ACE2 binding or facilitate escape from therapeutic antibodies (Harvey et al., 2021, Nature Reviews Microbiology).

Other names

SARS-CoV-2 RBD-ACE2 complexSpike-ACE2 interfaceSARS-CoV-2 S-RBD:hACE2 interfaceRBD-ACE2 PPI

Competitive inhibition of the protein-protein interaction between the viral spike RBD and the host ACE2 receptor, preventing viral attachment and entry into host cells (Taylor et al., 2021, Nature Reviews Genetics).