Severe acute respiratory syndrome coronavirus 2 XBB.1.5 spike protein (SARS-CoV-2 XBB.1.5 S protein) (SARS-CoV-2 XBB.1.5 S protein)

The SARS-CoV-2 XBB.1.5 spike protein is the primary surface glycoprotein of the XBB.1.5 subvariant, a recombinant of the BA.2.10.1 and BA.2.75 lineages within the Omicron family (CDC, 2023). It is the essential mediator of viral entry, utilizing its receptor-binding domain (RBD) to attach to the human Angiotensin-converting enzyme 2 (ACE2) receptor (UniProt P0DTC2). A critical F486P mutation in the RBD distinguishes XBB.1.5, providing a significant growth advantage through increased ACE2 binding affinity and potent immune evasion (Yue et al., Nature, 2023). This protein serves as the foundational antigen for the 2023-2024 monovalent COVID-19 vaccines, designed to elicit neutralizing antibodies that prevent host cell infection (FDA, 2023). Despite its role as a vaccine target, the protein's rapid evolution has led to the loss of clinical efficacy for most previously authorized monoclonal antibodies, such as tixagevimab/cilgavimab (Wang et al., Cell, 2023). Consequently, it remains a focal point for the development of next-generation therapeutics and surveillance of viral fitness.

Other names

Omicron XBB.1.5 spike proteinKraken variant spike proteinSARS-CoV-2 S protein (XBB.1.5)Spike glycoprotein (XBB.1.5)SARS-CoV-2 XBB.1.5 S glycoprotein

The target is utilized in vaccines to induce neutralizing antibodies and T-cell responses; these antibodies bind to the spike protein's receptor-binding domain, sterically hindering its interaction with the host ACE2 receptor and preventing viral entry (FDA, 2023; Yue et al., Nature, 2023).