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

The SARS-CoV-2 spike (S) protein is a large trimeric glycoprotein that mediates viral entry into host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor [10, 11]. The Omicron BA.4 and BA.5 subvariants share an identical spike protein sequence, which is characterized by key mutations such as L452R, F486V, and the R493Q reversion [1, 2, 7]. These mutations enhance the protein's affinity for ACE2 and significantly increase its ability to evade neutralizing antibodies elicited by previous infections or ancestral-strain vaccines [3, 4, 9]. As a primary target for therapeutic intervention, the BA.4/BA.5 spike protein has driven the development of bivalent mRNA vaccines designed to provide broader protection against evolving variants [12]. However, the rapid accumulation of mutations in the receptor-binding domain (RBD) poses a continuous challenge for monoclonal antibody therapies, many of which have lost clinical efficacy against these subvariants [4, 7, 9].

Other names

Spike proteinS proteinSurface glycoproteinOmicron BA.4/BA.5 spikeB.1.1.529.4 spikeB.1.1.529.5 spike

The mechanism of action for drugs targeting the SARS-CoV-2 spike protein involves the inhibition of viral entry into host cells. Monoclonal antibodies bind to the receptor-binding domain (RBD) or N-terminal domain (NTD) of the spike protein, thereby blocking its interaction with the host angiotensin-converting enzyme 2 (ACE2) receptor or preventing the structural rearrangements required for membrane fusion [10, 11, 13]. Vaccines utilize the spike protein sequence to stimulate the host immune system to produce neutralizing antibodies and activate T-cell responses, providing prophylactic protection against infection and reducing the risk of severe disease [3, 11, 12].