Understanding Human Coronavirus HCoV-NL63

Abdul-Rasool, Sahar; Fielding, Burtram C

The species tropism and virulence of a particular coronavirus are largely determined by the spike (S) glycoprotein. Coronavirus S proteins mediate attachment to the cellular receptors and subsequent fusion of the virus and cell membrane [20] . The N-terminal portion of HCoV-NL63 S contains a unique 179 amino acid domain not present in other coronaviruses. This region represents the most variable region of the HCoV-NL63 genome and a role in immune evasion for this region has been proposed [8, 27] . HCoV-NL63 S is a single-chain glycoprotein and consists of an Nterminal receptor-binding domain (S1) and a C-terminal transmembrane fusion domain (S2). S2 consists of two highly conserved heptad-repeat (HR) sequences that are larger than the corresponding regions for the group II and group III coronaviruses [20, 27, 33] . Initial proteolytic studies of the S2 fusion core identified an -helical domain consisting of a trimer of the HR segments N57 and C42. The resolved crystal structure of this trimeric complex shows distinctive high-affinity conformations of interacting crosssectional layers of six helices. It has been suggested that the larger HR regions of the group I coronaviruses may be required to prime the S proteins for their fusion-activating conformational changes during entry of the virus [20] .