SpikeProteins

SpikeProteins are viral envelope glycoproteins that mediate attachment and entry of enveloped viruses into host cells. In coronaviruses such as SARS-CoV-2, SpikeProteins assemble into a trimer that projects from the viral surface and comprises two functional subunits: S1, which binds the host receptor, and S2, which promotes membrane fusion. The receptor-binding domain within S1 engages the ACE2 receptor in SARS-CoV-2 and related receptors in other coronaviruses. Activation requires proteolytic cleavage by host proteases at the S1/S2 and S2' sites, enabling the conformational changes that drive fusion of viral and cellular membranes. SpikeProteins are class I fusion proteins and are heavily glycosylated, contributing to a glycan shield that shapes antigenicity. The prefusion form is metastable and has been stabilized in vaccines by substitutions such as proline residues to improve immunogenicity. Functionally, SpikeProteins determine host range and tissue tropism through receptor binding, and they are the primary targets of neutralizing antibodies. Antigenic variation in SpikeProteins can alter receptor affinity and immune recognition, influencing the emergence of variants of concern. In research and medicine, SpikeProteins are central to vaccines and serological assays; many vaccines encode stabilized Spike proteins to elicit protective antibodies, and assays commonly measure responses to Spike. Structural biology studies reveal multiple conformations and inform design of immunogens. Genetic variation, recombination, and selective pressures continue to shape SpikeProteins across coronaviruses.