SARS-CoV-2 XBB.1.5 spike–Angiotensin-converting enzyme 2 protein–protein interface (SARS-CoV-2 XBB.1.5 S–ACE2 PPI)

The SARS-CoV-2 XBB.1.5 spike–Angiotensin-converting enzyme 2 (ACE2) protein–protein interface is the primary molecular gateway for the entry of the XBB.1.5 variant into human cells. This interface is formed by the interaction between the Receptor Binding Domain (RBD) of the viral spike protein and the extracellular peptidase domain of the human ACE2 receptor (Yue et al., Nature, 2023). XBB.1.5 is distinguished by the F486P mutation, which significantly enhances its binding affinity to ACE2 compared to previous Omicron subvariants, facilitating its rapid global spread (Wang et al., Lancet Infectious Diseases, 2023). As a therapeutic target, this interface is the focus of updated mRNA vaccines and next-generation monoclonal antibodies designed to neutralize the virus by sterically hindering the S-ACE2 interaction (Ito et al., Journal of Medical Virology, 2023). However, the interface is a hotspot for mutational escape, which has rendered most previously authorized monoclonal antibodies, such as Bebtelovimab and Sotrovimab, largely ineffective against this specific variant (Miller et al., New England Journal of Medicine, 2023). Consequently, the interface remains a critical area of study for developing broad-spectrum therapeutics that can withstand the virus's continued evolution. The structural stability of this complex is a key determinant of viral infectivity and host range. Therapeutic strategies targeting this PPI aim to prevent the conformational changes required for membrane fusion.

Other names

XBB.1.5 Spike-ACE2 interfaceSARS-CoV-2 XBB.1.5 RBD-ACE2 complexXBB.1.5 S-ACE2 interactionKraken variant spike-ACE2 interface

Inhibition of viral entry by blocking the interaction between the viral spike protein and the host ACE2 receptor.