Spikes or spike proteins are typical components of virion and viruses. They are also called peplomers and belong to class I fusion proteins. Usually composed of more than one thousand aminoacids, these rod-shaped molecules point out of the virus envelope. Spikes often assemble as highly glycosylated dimers or trimers bearing mainly N-glycosylations and O-glycosylations. They are found at the surface of different viruses and especially on the coronaviruses, including SARS-CoV-2. As membrane proteins they can be separated into several subdomains. The ectodomains contains the S1 domain which includes the Receptor Binding Domain (RBD) and the main part of the S2 domain which C-Terminal is in the membrane domain.
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Spike and RBD function
Spike proteins mediate the adhesion and entry of the virus into its target cells. The spike interacts with membrane receptors at the cell surface. The S1 region is responsible for this activity. The receptor binding domain (RBD protein) is the subdomain that recognizes its receptor target. It may be of different kind. In the case of SARS-CoV and SARS-CoV-2, the angiotensin-converting enzyme 2 (ACE2) is the host protein targeted by the virus. Thus, the spike is responsible for the definition of hosts and host cells the virus targets. The Spike protein then fuses the membranes of the cell and virus. The S2 protein is responsible of this second activity thanks to its fusion peptide that destabilizes the host cell membrane. The S2 region also contains the transmembrane subdomain in the C-Terminal of the spike protein. The spike protein undergoes a wide conformational change upon fusion with the host which enables the viral RNA genome to enter the host cell. This conformation change depends on many triggers depending on the virus type and local environment.
Spike proteins and especially RBDs are highly immunogenic. Antibodies found in infected individuals are mostly directed against the RBD.
The SARS-CoV-2 spikes have mutated many times during the COVID-19 pandemic leading to different variants. Sets of mutations in the RBD region have been further associated with immunogenic properties such as transmissibility or infectivity. Looking for RBD variants? Find the most complete list of variants that emerged since the beginning of the pandemic on our online shop.