SARS-CoV-1 spike (S3a) protein, as a component of the S3:M:E:encapsidated SARS coronavirus genomic RNA: 7a:O-glycosyl 3a tetramer complex, binds to glycosylated angiotensin converting enzyme 2 (ACE2) associated with the human host cell plasma membrane. Structural studies of the interaction between human ACE2 protein and the receptor-binding domain of S3a protein have identified key amino acid residues in both proteins responsible for their high-affinity interaction. These residues may be a key factor determining severity (and possibly human-to-human transmission) of SARS-CoV-1 (Li et al. 2003, 2005). The roles of S protein in viral binding to the host cell membrane and fusion of viral and host cell membranes and thus the central role of S protein in determining the host range and tissue tropisms of the virus are reviewed by Belouzard et al. (2012).