As is the case for other β-coronavirus S glycoproteins, including SARS-CoV S, the S1 subunit has a V-shaped architecture. In the closed S trimer, the three hACE2-recognition motifs, whose location was inferred based on the crystal structure of SARS-CoV SB in complex with hACE2, are buried at the interface between protomers. As a result, SARS-CoV-2 SB opening  is expected to be necessary for interacting with ACE2 at the host cell surface and initiating the conformational changes leading to cleavage  of the S2′ site, membrane fusion and viral entry.