The envelope-anchored trimeric spike protein mediates coronavirus entry into host cells by binding to its host receptor and subsequently fusing host and viral membranes.

Coronavirus S proteins, including SARS-S, share several features: Peplomers of coronavirus S proteins protrude from the virion surface and are responsible for the corona-like shape of virions observed upon electron microscopy.

A hallmark of these proteins is the presence of an N-terminal surface unit (termed S1 in the context of CoV S proteins), which harbors the receptor binding domain and a C-terminal transmembrane unit (termed S2 in the context of CoV S proteins), which contains the functional elements required for membrane fusion: a fusion peptide, heptad repeats and a transmembrane domain.
A second characteristic shared by class I membrane fusion proteins is the transition of the transmembrane unit into a thermostable, protease-insensitive conformation termed six-helix-bundle upon successful completion of the membrane fusion reaction.he first indispensable step of the entry cascade is the binding of the S proteins to a receptor.
Upon activation, a fusion peptide located at the N-terminus of the S2 subunit inserts into a target cell membrane, either the plasma membrane or an endosomal membrane.

The receptor binding domain (RBD) of SARS-S is located at the C-terminus of the S1 subunit and binds to ACE2 with high affinity. The RBD consists of two subdomains, a core and an extended loop. The core structure is conserved between SARS-S and other CoV S proteins but is not directly involved in ACE2 binding.Whether a host is susceptible to SARS-CoV is largely determined by the binding affinity between SARS-CoV RBD and host ACE2 in the initial step of viral attachment

Upon activation, a fusion peptide located at the N-terminus of the S2 subunit inserts into a target cell membrane. The S2 subunit is connected with the viral membrane via its transmembrane domain and the cellular membrane via the fusion peptide