| + |
CTSL | up-regulates activity 
cleavage
|
S |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260218 |
|
|
in vitro |
|
| pmid |
sentence |
| 16081529 |
A cell-free membrane-fusion system demonstrates that engagement of receptor followed by proteolysis is required for SARS-CoV membrane fusion and indicates that cathepsin L is sufficient to activate membrane fusion by SARS-CoV S. These results suggest that SARS-CoV infection results from a unique, three-step process: receptor binding and induced conformational changes in S glycoprotein followed by cathepsin L proteolysis within endosomes. The requirement for cathepsin L proteolysis identifies a previously uncharacterized class of inhibitor for SARS-CoV infection. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| Pathways: | COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY |
| + |
MBL2 | down-regulates activity 
binding
|
S |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260285 |
|
|
Homo sapiens |
THP-1 Cell |
| pmid |
sentence |
| 20573835 |
We have demonstrated that MBL selectively binds to SARS-S pseudotyped virus and can inhibit SARS-CoV infection in susceptible cell lines. Our results identified a single N-linked glycosylation site, N330, on S glycoprotein as the target for the specific interactions between MBL and SARS-CoV and provide evidence that the viral interaction with MBL did not affect its interaction with the ACE2 receptor. Binding to MBL did not affect SARS-S interactions with the ACE2 receptor. Furthermore, MBL-mediated inhibition occurred at a step prior to CTSL-mediated activation of SARS-S fusion. Thus, we suggest that the binding of the MBL may interfere with the induction of conformational changes within the S glycoprotein and thus prevent an early, postreceptor-binding event. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
IFITMs | down-regulates activity 
|
S |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260230 |
|
|
Homo sapiens |
HEK-293 Cell, Huh-7.5 Cell |
| pmid |
sentence |
| 29263263 |
All three IFITMs significantly inhibited the infection by lentiviral particles pseudotyped with IAV hemagglutinin 1 (H1) and neuraminidase 1 (N1) (IAVpp), Spike protein (S) of HCoV-229E (229Epp), HCoV-NL63 (NL63pp), SARS-CoV (SARSpp), and MERS-CoV (MERSpp) in both HEK293 (Fig. 1B) and Huh7.5 (Fig. 1C) cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260217 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 32142651 |
Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY |
| + |
S | down-regulates activity
binding
|
ACE2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260283 |
|
|
Chlorocebus aethiops |
|
| pmid |
sentence |
| 18554741 |
Cell entry of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by the viral spike (S) protein. Amino acids 319-510 on the S protein have been mapped as the receptor-binding domain (RBD), which mediates binding to the SARS-CoV receptor angiotensin converting enzyme 2 (ACE2) on SARS-CoV susceptible cells. Here, we demonstrate that the RBD spike protein alone can be internalized together with ACE2. We propose that after binding to ACE2, the RBD spike protein activates the ACE2 mediated cellular endocytosis signal pathway, by which SARS-CoV enters the susceptible cells. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260216 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14670965 |
The coronavirus spike (S) protein mediates infection of receptor-expressing host cells and is a critical target for antiviral neutralizing antibodies. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for the coronavirus (severe acute respiratory syndrome (SARS)-CoV) that causes SARS. Here we demonstrate that a 193-amino acid fragment of the S protein (residues 318-510) bound ACE2 more efficiently than did the full S1 domain (residues 12-672). Smaller S protein fragments, expressing residues 327-510 or 318-490, did not detectably bind ACE2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260291 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16988814 |
In acute lung injury, such as acid aspiration, pneumonia, or sepsis, the generation of ANG II from ANG I is enhanced by ACE, and ANG II induces acute lung failure through stimulation of the AT1 receptor, while ACE2 and ANG II type 2 receptor negatively regulate this pathway and protect from acute lung failure. On the other hand, SARS-CoV infection is mediated through binding of the SARS-Spike protein to ACE2 or L-SIGN and down-regulates the protective molecule ACE2, and thus leads to severe lung injury and acute lung failure |
|
| Publications: |
3 |
Organism: |
Chlorocebus Aethiops, Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY, SARS-CoV FIBROSIS |
| + |
S | up-regulates activity
binding
|
CLEC4M |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260269 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15479853 |
Here we show that DC-SIGN and DC-SIGNR enhance infection mediated by the glycoprotein (GP) of Marburg virus (MARV) and the S protein of severe acute respiratory syndrome coronavirus and might promote viral dissemination. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
S | up-regulates activity
binding
|
CD209 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260270 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15479853 |
Here we show that DC-SIGN and DC-SIGNR enhance infection mediated by the glycoprotein (GP) of Marburg virus (MARV) and the S protein of severe acute respiratory syndrome coronavirus and might promote viral dissemination. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
S | form complex 
binding
|
Spike protein-ACE2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260287 |
|
|
Chlorocebus aethiops |
Vero Cell |
| pmid |
sentence |
| 18554741 |
Cell entry of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by the viral spike (S) protein. Amino acids 319-510 on the S protein have been mapped as the receptor-binding domain (RBD), which mediates binding to the SARS-CoV receptor angiotensin converting enzyme 2 (ACE2) on SARS-CoV susceptible cells. Here, we demonstrate that the RBD spike protein alone can be internalized together with ACE2. We propose that after binding to ACE2, the RBD spike protein activates the ACE2 mediated cellular endocytosis signal pathway, by which SARS-CoV enters the susceptible cells. |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| Pathways: | SARS-CoV ATTACHMENT AND ENTRY |
| + |
S | up-regulates 
|
Apoptosis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260219 |
|
|
Chlorocebus aethiops |
Vero Cell |
| pmid |
sentence |
| 16310778 |
We demonstrated that the adenovirus-mediated over-expression of SARS-CoV spike (S) protein and its C-terminal domain (S2) induce apoptosis in Vero E6 cells in a time- and dosage-dependent manner |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| Pathways: | COVID-19 Causal Network, SARS-COV APOPTOSIS, SARS-CoV FIBROSIS, SARS-CoV ER STRESS |
| + |
S | down-regulates activity
binding
|
EIF3F |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260255 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18231581 |
Coronavirus spike protein inhibits host cell translation by interaction with eIF3f |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
S | up-regulates activity
|
EIF2AK3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260439 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16940539 |
SARS-CoV S protein specifically activated PERK but did not significantly affect IRE1/XBP1 or ATF6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV ER STRESS |
| + |
S | up-regulates activity
binding
|
TLR2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260972 |
|
|
Homo sapiens |
Peripheral Blood Mononuclear Cell |
| pmid |
sentence |
| 19185596 |
S protein is a ligand for human TLR2. S protein utilizes toll-like receptor 2(TLR 2) to increase IL-8 production.Our results show that SARS S protein in a soluble form increased IL-8 production through hTLR2 ligand interaction. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | SARS-CoV CYTOKINE STORM |
| + |
S | up-regulates quantity
|
TNF |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260280 |
|
|
Homo sapiens |
Macrophage |
| pmid |
sentence |
| 17412287 |
The ability of S-protein to induce TNF-a |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-COV APOPTOSIS, SARS-CoV CYTOKINE STORM, SARS-CoV INFLAMMATORY RESPONSE |
| + |
S | up-regulates quantity
|
IL6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260278 |
|
|
Homo sapiens |
Macrophage |
| pmid |
sentence |
| 17412287 |
The ability of S-protein to induce TNF-a |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV CYTOKINE STORM |
| + |
S | up-regulates quantity by expression
transcriptional regulation
|
HSPA5 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260351 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16940539 |
Perturbation of the function of endoplasmic reticulum (ER) causes stress leading to the activation of cell signaling pathways known as the unfolded protein response (UPR). Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) uses ER as a site for synthesis and processing of viral proteins. In this report, we demonstrate that infection with SARS-CoV induces the UPR in cultured cells. A comparison with M, E, and NSP6 proteins indicates that SARS-CoV spike (S) protein sufficiently induces transcriptional activation of several UPR effectors, including glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV ER STRESS |
| + |
S | up-regulates quantity
|
CXCL8 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260279 |
|
|
Homo sapiens |
Macrophage |
| pmid |
sentence |
| 17412287 |
The ability of S-protein to induce TNF-a |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | SARS-CoV CYTOKINE STORM |
| + |
S | up-regulates quantity by expression
transcriptional regulation
|
HSP90B1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260352 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16940539 |
Perturbation of the function of endoplasmic reticulum (ER) causes stress leading to the activation of cell signaling pathways known as the unfolded protein response (UPR). Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) uses ER as a site for synthesis and processing of viral proteins. In this report, we demonstrate that infection with SARS-CoV induces the UPR in cultured cells. A comparison with M, E, and NSP6 proteins indicates that SARS-CoV spike (S) protein sufficiently induces transcriptional activation of several UPR effectors, including glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
S | down-regulates quantity by repression
transcriptional regulation
|
ATF6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260349 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31226023 |
Activation of the ATF6 pathway by HCoV infection is less studied, and most studies have relied on indirect methods, such as luciferase reporter, due to the lack of a specific antibody. No ATF6 cleavage was detected in cells infected with SARS-CoV, and overexpression of SARSCoV S protein failed to activate ATF6 luciferase reporter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV ER STRESS |
| + |
S | up-regulates activity
transcriptional regulation
|
PTGS2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262315 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17267381 |
Spike protein of SARS‐CoV activated COX‐2 expression in a protein concentration‐dependent manner |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | SARS-CoV INFLAMMATORY RESPONSE |
| + |
S | up-regulates quantity by expression
transcriptional regulation
|
DDIT3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260353 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16940539 |
Perturbation of the function of endoplasmic reticulum (ER) causes stress leading to the activation of cell signaling pathways known as the unfolded protein response (UPR). Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) uses ER as a site for synthesis and processing of viral proteins. In this report, we demonstrate that infection with SARS-CoV induces the UPR in cultured cells. A comparison with M, E, and NSP6 proteins indicates that SARS-CoV spike (S) protein sufficiently induces transcriptional activation of several UPR effectors, including glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV ER STRESS |
3.0
S
- 
- 