SARS-CoV-2 spike surface glycoprotein (S protein) (S protein)

The SARS-CoV-2 spike surface glycoprotein is a trimeric Class I fusion protein essential for viral entry into host cells (UniProt P0DTC2). It consists of two functional subunits: S1, which mediates binding to the host cell surface receptor angiotensin-converting enzyme 2 (ACE2), and S2, which facilitates the fusion of the viral and host cell membranes (PubMed: 32221306). This protein is the primary target for neutralizing antibodies produced during natural infection or following vaccination (NIH, 2023). Therapeutic interventions, such as monoclonal antibodies (e.g., Sotrovimab, Bebtelovimab), specifically target the receptor-binding domain (RBD) of the spike protein to block viral attachment (FDA, 2022). Due to its high exposure on the viral surface, it is subject to significant selective pressure, leading to mutations that characterize various SARS-CoV-2 variants of concern (WHO, 2024).

Other names

Spike proteinS proteinSurface glycoproteinSARS-CoV-2 S proteinSpike glycoprotein

Drugs targeting the spike protein, primarily monoclonal antibodies, act by binding to specific epitopes on the S1 subunit, particularly the receptor-binding domain (RBD). This binding sterically blocks the interaction between the spike protein and the human ACE2 receptor, preventing the virus from attaching to and entering host cells (StatPearls, 2023). Additionally, some antibodies may target the S2 subunit to inhibit the conformational changes required for membrane fusion.