Direct Host Cell Membrane Membrane Fusion and Release of SARS-CoV-2 Nucleocapsid

Stable Identifier
R-HSA-9698988
Type
Reaction [omitted]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
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SARS-CoV-2 virions attached to the host cell surface via a complex involving viral spike (S) protein and host angiotensin-converting enzyme 2 (ACE2) are inferred to undergo endocytosis. In the case of SARE-CoV-2 it is apparent that the spike protein undergoes cleavage in some cases and fuses directly with the plasma membrane. This cleavage is induced by FURIN or TMPRSS.
The cellular protease furin cleaves the spike protein at the S1/S2 site and that cleavage is essential for S-protein-mediated cell-cell fusion and entry into human lung cells (Hoffman et al. 2020).
Transmembrane protease serine 2 (TMPRSS2), associated with the plasma membrane of the host cell, mediates the hydrolytic cleavage of SARS-CoV-2 Spike (S) protein component of the viral membrane-associate S3:M:E:encapsidated SARS coronavirus genomic RNA: 7a:O-glycosyl 3a tetramer complex associated with ACE2 (Matsuyama et al. 2010; Glowacka et al. 2011; Shulla et al. 2011).
The uncoated virion nucleocapsid is released directly into the cytoplasm.

Literature References
PubMed ID Title Journal Year
21068237 A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry

Shulla, A, Heald-Sargent, T, Subramanya, G, Zhao, J, Perlman, S, Gallagher, T

J. Virol. 2011
32532959 The role of furin cleavage site in SARS-CoV-2 spike protein-mediated membrane fusion in the presence or absence of trypsin

Xia, S, Lan, Q, Su, S, Wang, X, Xu, W, Liu, Z, Zhu, Y, Wang, Q, Lu, L, Jiang, S

Signal Transduct Target Ther 2020
21325420 Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response

Glowacka, I, Bertram, S, Müller, MA, Allen, P, Soilleux, E, Pfefferle, S, Steffen, I, Tsegaye, TS, He, Y, Gnirss, K, Niemeyer, D, Schneider, H, Drosten, C, Pöhlmann, S

J. Virol. 2011
32362314 A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells

Hoffmann, M, Kleine-Weber, H, Pöhlmann, S

Mol. Cell 2020
15474033 Efficient assembly and release of SARS coronavirus-like particles by a heterologous expression system

Mortola, E, Roy, P

FEBS Lett. 2004
Participants
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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
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