Severe acute respiratory syndrome coronavirus 2 Omicron variant spike protein (SARS-CoV-2 Omicron S protein)

The SARS-CoV-2 Omicron variant spike protein is the primary surface component of the B.1.1.529 lineage and its subsequent subvariants, distinguished by a high density of mutations—over 30 in the spike region alone—compared to the ancestral strain [1]. It is a class I fusion protein that initiates infection by utilizing its receptor-binding domain (RBD) to attach to the human Angiotensin-Converting Enzyme 2 (ACE2) receptor [2]. This binding event triggers a conformational change that allows the protein to fuse the viral envelope with the host cell membrane, facilitating the release of the viral genome [3]. As the dominant target for the host's humoral immune response, the Omicron spike protein has evolved to significantly evade neutralizing antibodies generated by previous infections or early-generation vaccines [4]. Consequently, while it remains the central target for therapeutic monoclonal antibodies and vaccine development, many previously effective treatments have required re-evaluation or replacement due to the protein's rapid antigenic evolution [5]. Understanding the structural modifications of the Omicron spike is essential for the design of broad-spectrum COVID-19 therapeutics and variant-proof vaccines [6].

Other names

SARS-CoV-2 B.1.1.529 spike proteinOmicron variant surface glycoproteinSpike glycoprotein (SARS-CoV-2 Omicron)SARS-CoV-2 S protein (Omicron)

Neutralization of viral entry by competitively binding to the receptor-binding domain (RBD) or N-terminal domain (NTD) to sterically block interaction with host Angiotensin-Converting Enzyme 2 (ACE2) or by preventing the structural transitions required for membrane fusion.