Attachment and Entry

Coronavirus replication is initiated by the binding of S protein to the cell surface receptor(s). The S protein is composed of two functional domains, S1 (bulb) which mediates receptor binding and S2 (stalk) which mediates membrane fusion. Specific interaction between S1 and the cognate receptor triggers a drastic conformational change in S2, leading to fusion between the virus envelope and the cellular membrane and release of the viral nucleocapsid into the host cell cytosol. Receptor binding is the major determinant of the host range and tissue tropism for a coronavirus. Some human coronaviruses (HCoVs ) have adopted cell surface enzymes as receptors, angiotensin converting enzyme 2 (ACE2) for SARS-CoV-1 and HCoV NL63. The receptor-bound S protein is activated by cleavage into S1 and S2, mediated by one of two of two host proteases, the endosomal cysteine protease cathepsin L and another trypsin like serine protease. Type II transmembrane serine proteases TMPRSS2 and TMPRSS11D have also been implicated in the activation of S protein of SARS-CoV-1. Host factors may play additional roles in viral entry (not annotated here). Valosin containing protein (VCP) contributes by a poorly understood mechanism to the release of coronavirus from early endosomes. Host factors may also restrict the attachment and entry of HCoV. Some interferon inducible transmembrane proteins (IFITMs) exhibited broad spectrum antiviral functions against various RNA viruses including SARS-CoV-1 while others may facilitate HCoV entry into host cells.

Summary from Reactome (R-HSA-9678110), read 2026-09-23.