SARS-CoV-2 spike glycoprotein (Omicron lineage) (S protein (Omicron))

The SARS-CoV-2 spike (S) glycoprotein is a large, homotrimeric class I fusion protein located on the viral envelope, serving as the primary mediator of host cell entry [1, 4]. In the Omicron lineage (B.1.1.529 and its subvariants like BA.1, BA.5, XBB, and JN.1), the protein is characterized by an unusually high number of mutations, particularly within the receptor-binding domain (RBD) and the N-terminal domain (NTD) [2, 6]. These mutations enhance the protein's affinity for the human angiotensin-converting enzyme 2 (ACE2) receptor and facilitate extensive evasion of neutralizing antibodies elicited by previous infection or vaccination [4, 6]. As the principal target for both naturally induced immunity and therapeutic interventions, the Omicron spike protein's rapid evolution presents a continuous challenge for the development of effective monoclonal antibodies and updated vaccine formulations [3, 5]. Therapeutic strategies primarily focus on neutralizing the virus by blocking the RBD-ACE2 interaction or inhibiting the conformational changes required for membrane fusion [1, 4]. Recent evidence also suggests that persistent spike protein fragments may play a role in the pathogenesis of Long COVID [2].

Other names

Spike proteinS proteinSurface glycoproteinOmicron spikeB.1.1.529 spikeBA.1 spikeBA.2 spikeBA.5 spikeXBB spikeJN.1 spike

Neutralization of viral entry by blocking the interaction between the viral receptor-binding domain (RBD) and the host angiotensin-converting enzyme 2 (ACE2) receptor, or by inhibiting the S2-mediated membrane fusion process [1, 4, 6].