SARS-CoV-2 Omicron BA.5 spike glycoprotein (S protein (BA.5))

The SARS-CoV-2 Omicron BA.5 spike glycoprotein is a trimeric Class I fusion protein that mediates viral entry into host cells by binding to the human angiotensin-converting enzyme 2 (ACE2) receptor (1.1.2, 1.1.3). It consists of two subunits: S1, which contains the receptor-binding domain (RBD), and S2, which facilitates the fusion of the viral envelope with the host cell membrane (1.1.1, 1.1.4). The BA.5 variant is characterized by specific mutations, such as L452R and F486V, which enhance its binding affinity to ACE2 and significantly contribute to its ability to evade neutralizing antibodies from both prior infections and early-generation vaccines (1.2.1, 1.2.4). This protein is the primary target for COVID-19 vaccines, including the bivalent mRNA-1273.222 and BNT162b2 formulations designed to provide broader protection against Omicron subvariants (1.4.3, 1.4.4). While monoclonal antibodies like bebtelovimab initially showed activity against BA.5, the rapid evolution of the spike protein has led to the loss of efficacy for many previously authorized therapeutic antibodies, such as tixagevimab/cilgavimab (1.2.4, 1.4.2). Understanding the structural dynamics of the BA.5 spike is essential for developing next-generation entry inhibitors and monitoring the ongoing evolution of the virus (1.2.3, 1.3.1).

Other names

Spike proteinS proteinSurface glycoproteinSpike protein (BA.5 variant)SARS-CoV-2 S protein

Neutralization of viral entry by blocking the interaction between the spike protein's receptor-binding domain (RBD) and the host ACE2 receptor.