SpikeProtein

Spike protein, or S protein, is a transmembrane glycoprotein on the surface of coronaviruses. It is a trimeric class I fusion protein responsible for attachment to host cells and fusion of viral and cellular membranes. The spike gene S encodes a precursor that is cleaved into two subunits, S1 and S2. S1 contains the receptor-binding domain, which recognizes the host cell receptor, and an N-terminal domain that contributes to receptor engagement and antigenicity. S2 houses the fusion machinery, including the fusion peptide, heptad repeats HR1 and HR2, the transmembrane domain, and the cytoplasmic tail. The protein is heavily glycosylated, contributing to the glycan shield that can modulate immune recognition.

During entry, the spike protein binds its receptor (for SARS-CoV-2, ACE2), and host proteases cleave at the S1/S2 and S2' sites. Cleavage events and receptor binding trigger large-scale rearrangements of the S2 subunit, driving fusion of the viral envelope with the host membrane. The protein can adopt open (RBD-up) and closed (RBD-down) conformations, affecting receptor accessibility. Entry can occur at the cell surface, aided by TMPRSS2, or via endosomal routes with cathepsins, depending on the cell type and virus variant.

Spike proteins are central to vaccines and antibody responses, being the main target of neutralizing antibodies. Variants interest researchers due to mutations in the RBD and NTD that can alter receptor affinity and antibody recognition. Structural and functional studies using cryo-electron microscopy and pseudotyped particles support antigen design, diagnostics, and surveillance of variant lineages. While the spike protein is best characterized in SARS-CoV-2, other coronaviruses encode similar trimeric proteins that mediate entry.