Attachment and Entry

Stable Identifier
R-HSA-9694614
Type
Pathway
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
ReviewStatus
5/5
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This COVID-19 event has been created by a combination of computational inference (see https://reactome.org/documentation/inferred-events) from SARS-CoV-1 data and manual curation, as described in the summation for the overall SARS-CoV-2 infection pathway.

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-2 (reviewed by Jackson et al, 2022), SARS-CoV-1, and HCoV NL63. The receptor-bound S protein is activated by cleavage into S1 and S2, mediated by one 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-2. 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.
Literature References
PubMed ID Title Journal Year
31226023 Human Coronavirus: Host-Pathogen Interaction

Fung, TS, Liu, DX

Annu. Rev. Microbiol. 2019
34611326 Mechanisms of SARS-CoV-2 entry into cells

Jackson, CB, Farzan, M, Choe, H, Chen, B

Nat Rev Mol Cell Biol 2022
Participants
Participates
Inferred From
Disease
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
Authored
Reviewed
Created
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