SARS-CoV-2 Omicron XBB.1.5 spike protein receptor-binding domain and human angiotensin-converting enzyme 2 interface (SARS-CoV-2 XBB.1.5 RBD/hACE2 interface)

The SARS-CoV-2 Omicron XBB.1.5 spike protein receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (hACE2) interface is the primary molecular site for viral attachment and entry into host cells. This interface is characterized by specific mutations in the XBB.1.5 variant, most notably the F486P substitution, which significantly increases its binding affinity for the hACE2 receptor compared to earlier Omicron subvariants (Yue et al., 2023). As the critical gateway for infection, this protein-protein interaction interface is the main target for neutralizing antibodies elicited by vaccination or natural infection. However, the extensive mutations within the XBB.1.5 RBD facilitate substantial immune evasion, rendering many previously authorized monoclonal antibodies, such as Bebtelovimab and the Tixagevimab/Cilgavimab combination, largely ineffective (Wang et al., 2023). Consequently, therapeutic and prophylactic efforts have shifted toward updated mRNA vaccines specifically designed to match the XBB.1.5 spike sequence (CDC, 2023). Monitoring the structural changes at this interface is essential for predicting the efficacy of current biologics and for the development of next-generation pan-sarbecovirus therapies. The interface also serves as a focal point for diagnostic assays and the assessment of neutralizing antibody titers in clinical settings (Ito et al., 2023). Understanding the thermodynamics and kinetics of this interaction helps in identifying conserved epitopes that may be less prone to mutational escape.

Other names

SARS-CoV-2 XBB.1.5 RBD-hACE2 complexOmicron XBB.1.5 spike-ACE2 interfaceKraken variant RBD-ACE2 interface

Neutralization of viral entry by blocking the interaction between the viral receptor-binding domain and the host ACE2 receptor; induction of humoral immunity through vaccine-mediated antibody production.