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SARS-CoV-2 Spike

The newly identified 2019 novel coronavirus (SARS-CoV-2) has caused more than 11,900 laboratory-confirmed human infections, including 259 deaths, posing a serious threat to human health.
Full Name
SARS-CoV-2 Spike
Function
Spike protein S1
Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2 (PubMed:32142651, PubMed:33607086, PubMed:32155444).
When S2/S2' has been cleaved, binding to the receptor triggers direct fusion at the cell membrane (PubMed:34561887).
When S2/S2' has not been cleaved, binding to the receptor results in internalization of the virus by endocytosis leading to fusion of the virion membrane with the host endosomal membrane (PubMed:32221306, PubMed:32075877).
Alternatively, may use NRP1/NRP2 (PubMed:33082294, PubMed:33082293) and integrin as entry receptors (PubMed:35150743).
The use of NRP1/NRP2 receptors may explain the tropism of the virus in human olfactory epithelial cells, which express these molecules at high levels but ACE2 at low levels (PubMed:33082293).
The stalk domain of S contains three hinges, giving the head unexpected orientational freedom (PubMed:32817270).
Spike protein S2
Precursor of the fusion protein processed in the biosynthesis of the S protein and the formation of virus particle. Mediates fusion of the virion and cellular membranes by functioning as a class I viral fusion protein. Contains two viral fusion peptides that are unmasked after cleavage. The S2/S2' cleavage occurs during virus entry at the cell membrane by host TMPRSS2 (PubMed:32142651) or during endocytosis by host CSTL (PubMed:32703818, PubMed:34159616).
In either case, this triggers an extensive and irreversible conformational change leading to fusion of the viral envelope with the cellular cytoplasmic membrane, releasing viral genomic RNA into the host cell cytoplasm (PubMed:34561887).
Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of the viral and target cell membranes, the coiled coil regions (heptad repeats) adopt a trimer-of-hairpins structure and position the fusion peptide in close proximity to the C-terminal region of the ectodomain. Formation of this structure appears to promote apposition and subsequent fusion of viral and target cell membranes.
Spike protein S2'
Subunit of the fusion protein that is processed upon entry into the host cell. Mediates fusion of the virion and cellular membranes by functioning as a class I viral fusion protein. Contains a viral fusion peptide that is unmasked after S2 cleavage. This cleavage can occur at the cell membrane by host TMPRSS2 or during endocytosis by host CSTL (PubMed:32703818, PubMed:34159616).
In either case, this triggers an extensive and irreversible conformational change that leads to fusion of the viral envelope with the cellular cytoplasmic membrane, releasing viral genomic RNA into the host cell cytoplasm (PubMed:34561887).
Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of the viral and target cell membranes, the coiled coil regions (heptad repeats) adopt a trimer-of-hairpins structure and position the fusion peptide in close proximity to the C-terminal region of the ectodomain. Formation of this structure appears to promote apposition and subsequent fusion of viral and target cell membranes.
Biological Process
Biological Process fusion of virus membrane with host endosome membraneIEA:UniProtKB-UniRule
Biological Process fusion of virus membrane with host plasma membraneIEA:UniProtKB-UniRule
Biological Process membrane fusionManual Assertion Based On ExperimentIDA:ComplexPortal
Biological Process positive regulation of viral entry into host cell1 PublicationIC:ComplexPortal
Biological Process receptor-mediated endocytosis of virus by host cellManual Assertion Based On ExperimentIDA:DisProt
Biological Process receptor-mediated virion attachment to host cell1 PublicationIDA:UniProtKB
Biological Process suppression by virus of host tetherin activityIEA:UniProtKB-KW
Biological Process suppression by virus of host type I interferon-mediated signaling pathwayIEA:UniProtKB-KW
Biological Process viral entry into host cellIDA:UniProtKB
Biological Process viral life cycleIC:ComplexPortal
Cellular Location
Virion membrane
Host endoplasmic reticulum-Golgi intermediate compartment membrane
Host cell membrane
Accumulates in the endoplasmic reticulum-Golgi intermediate compartment, where it participates in virus particle assembly. Some S oligomers are transported to the host plasma membrane, where they may mediate cell-cell fusion (PubMed:34504087).
An average of 26 +/-15 S trimers are found randomly distributed at the surface of the virion (PubMed:32979942).
Topology
Extracellular: 14-1213
Helical: 1214-1234
Cytoplasmic: 1235-1273
PTM
The cytoplasmic Cys-rich domain is palmitoylated. Palmitoylated spike proteins drive the formation of localized ordered cholesterol and sphingo-lipid-rich lipid nanodomains in the early Golgi, where viral budding occurs.
Specific enzymatic cleavages in vivo yield mature proteins. The precursor is processed into S1 and S2 by host furin or unknown proteases to yield the mature S1 and S2 proteins (PubMed:32362314, PubMed:32703818, PubMed:34159616, PubMed:34561887, PubMed:32155444).
Processing between S2 and S2' occurs either by host CTSL in endosomes (PubMed:32221306, PubMed:33465165, PubMed:34159616), or by host TMPRSS2 at the cell surface (PubMed:32142651).
Both cleavages are necessary for the protein to be fusion competent (PubMed:32703818, PubMed:34159616, PubMed:34561887).
Cell surface activation allows the virus to enter the cell despite inhibition of the endosomal pathway by hydroxychloroquine (PubMed:33465165).
The polybasic furin cleavage site is absent in SARS-CoV S (PubMed:32155444, PubMed:32362314, PubMed:33465165).
It increases the dependence on TMPRSS2 expression by SARS-CoV-2 (PubMed:33465165).
D614G substitution would enhance furin cleavage at the S1/S2 junction (PubMed:33417835).
Highly decorated by heterogeneous N-linked glycans protruding from the trimer surface (PubMed:32075877, PubMed:32155444, PubMed:32929138).
Highly glycosylated by host both on S1 and S2 subunits, occluding many regions across the surface of the protein (PubMed:32366695, PubMed:32363391, PubMed:32929138).
Approximately 40% of the protein surface is shielded from antibody recognition by glycans, with the notable exception of the ACE2 receptor binding domain (PubMed:32929138).
O-glycosylated by host GALNT1 at the end of S1. This could reduce the efficiency of S1/S2 cleavage.

Anti-SARS-CoV-2 Spike antibodies

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Target: SARS-CoV-2 Spike
Host: Mouse
Antibody Isotype: IgG1
Specificity: SARS Coronavirus, SARS Coronavirus 2
Clone: N01
Application*: ELISA, Neutralization
Target: SARS-CoV-2 Spike
Host: Mouse
Antibody Isotype: IgG2b
Specificity: SARS Coronavirus, SARS Coronavirus 2
Clone: N02
Application*: ELISA, Neutralization
Target: SARS-CoV-2 Spike
Host: Rabbit
Antibody Isotype: IgG
Specificity: SARS Coronavirus, SARS Coronavirus 2
Clone: N03
Application*: ELISA, Neutralization
Target: SARS-CoV-2 Spike
Host: Human
Antibody Isotype: IgG1
Specificity: SARS Coronavirus, SARS Coronavirus 2
Clone: CR3022
Application*: ELISA, Neutralization
Target: SARS-CoV-2 Spike
Host: Rabbit
Antibody Isotype: IgG
Specificity: 2019 Novel Coronavirus
Clone: CBFYR-0123
Application*: WB, ELISA, IHC-P, FC, IF, IP
Target: SARS-CoV-2 Spike
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: SARS Coronavirus, SARS Coronavirus 2
Clone: CBC001
Application*: WB, ICC/IF, FC
Target: SARS-CoV-2 Spike
Host: Human
Antibody Isotype: IgG1
Specificity: SARS Coronavirus, SARS Coronavirus 2
Clone: CBC005
Application*: ELISA, WB
For Research Use Only. Not For Clinical Use.
(P): Predicted
* Abbreviations
IFImmunofluorescence
IHImmunohistochemistry
IPImmunoprecipitation
WBWestern Blot
EELISA
MMicroarray
CIChromatin Immunoprecipitation
FFlow Cytometry
FNFunction Assay
IDImmunodiffusion
RRadioimmunoassay
TCTissue Culture
GSGel Supershift
NNeutralization
BBlocking
AActivation
IInhibition
DDepletion
ESELISpot
DBDot Blot
MCMass Cytometry/CyTOF
CTCytotoxicity
SStimulation
AGAgonist
APApoptosis
IMImmunomicroscopy
BABioassay
CSCostimulation
EMElectron Microscopy
IEImmunoelectrophoresis
PAPeptide Array
ICImmunocytochemistry
PEPeptide ELISA
MDMeDIP
SHIn situ hybridization
IAEnzyme Immunoassay
SEsandwich ELISA
PLProximity Ligation Assay
ECELISA(Cap)
EDELISA(Det)
BIBioimaging
IOImmunoassay
LFLateral Flow Immunoassay
LALuminex Assay
CImmunohistochemistry-Frozen Sections
PImmunohistologyp-Paraffin Sections
ISIntracellular Staining for Flow Cytometry
MSElectrophoretic Mobility Shift Assay
RIRNA Binding Protein Immunoprecipitation (RIP)
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