SARS-CoV-2 Omicron spike protein receptor-binding domain and human angiotensin-converting enzyme 2 complex (SARS-CoV-2 Omicron RBD-hACE2 complex)

The interaction between the SARS-CoV-2 Omicron variant spike glycoprotein receptor-binding domain (RBD) and the human angiotensin-converting enzyme 2 (ACE2) receptor is the primary mechanism for viral entry into host cells (Mannar et al., Science, 2022). The Omicron variant (B.1.1.529) is characterized by a high number of mutations in the RBD, which enhance its binding affinity to ACE2 and facilitate immune evasion from many existing neutralizing antibodies (Cui et al., Nature Communications, 2022). This protein-protein interaction (PPI) occurs when the RBD of the viral spike protein recognizes and binds to the peptidase domain of ACE2 on the surface of respiratory epithelial cells (UniProt P0DTC2, Q9BYF1). Following binding, the virus undergoes conformational changes that lead to membrane fusion and the release of viral RNA into the cytoplasm (NIH, 2023). Targeting this specific interaction is a major focus for the development of therapeutic monoclonal antibodies and small-molecule entry inhibitors (FDA, 2022). However, the rapid evolution of the Omicron lineage continues to challenge the efficacy of these interventions due to structural changes at the binding interface (Cao et al., Nature, 2022). Understanding the structural biology of this complex is crucial for designing variant-proof vaccines and therapeutics to combat COVID-19 (PubMed, 2023).

Other names

Omicron RBD-ACE2 interfaceSARS-CoV-2 B.1.1.529 spike RBD-ACE2 interactionSARS-CoV-2 Omicron S-RBD:hACE2 complexSARS-CoV-2 Omicron variant spike protein receptor-binding domain interaction with human angiotensin-converting enzyme 2

Neutralizing antibodies and entry inhibitors bind to the spike RBD, sterically hindering its ability to interact with the host ACE2 receptor, thereby preventing viral attachment and subsequent entry into the cell.