Severe acute respiratory syndrome coronavirus 2 spike glycoprotein S1 subunit (SARS-CoV-2 S1 protein or Spike S1)

The SARS-CoV-2 spike S1 protein is the receptor-binding subunit of the viral spike glycoprotein, forming the globular head of the trimeric spike complex that decorates the viral surface[1][2]. The S1 subunit contains the N-terminal domain (NTD) and receptor-binding domain (RBD), which together recognize and bind to the angiotensin-converting enzyme 2 (ACE2) receptor on host cells, initiating the first critical step of viral entry[1][3]. The protein is heavily glycosylated, containing 22 N-linked glycosylation sites that modulate immune responses and facilitate structural stability[1]. As the primary target for SARS-CoV-2 vaccines and therapeutic antibodies, the S1 protein has become central to pandemic response strategies. Vaccine development has focused on stabilizing the prefusion conformation of the spike protein through amino acid substitutions (such as the S-2P variant), enhancing both structural integrity and immunogenicity[3]. Multiple therapeutic modalities, including monoclonal antibodies and small-molecule entry inhibitors, target the S1 subunit to prevent viral attachment and entry into host cells, making it one of the most validated viral protein targets in recent medical history[1][8].

Other names

Spike protein S1 subunitSARS-CoV-2 S1Coronavirus spike S1Receptor-binding subunit

Receptor blocking: Antibodies and inhibitors prevent S1 from binding to ACE2 receptors on host cells. Immune activation: Vaccines use S1 protein or RBD to stimulate adaptive immune responses. Conformational stabilization: Vaccine designs use proline substitutions (S-2P variant) to stabilize the prefusion state and enhance immunogenicity.