| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T170 |
0-314 |
Sentence |
denotes |
Because of the sequence similarity between SARS-CoV and SARS-CoV-2, their affected receptor, and recently confirmed TMPRSS2-mediated viral entry, it is reasonable to hypothesize that SARS-CoV-2 may act similarly with respect to using host endocytosis machinery, subsequent virus propagation, and further infection. |
| T171 |
315-439 |
Sentence |
denotes |
Upon binding to ACE2, cleavage of the S protein at the S1/S2 sites and S2 allows for fusion of viral and cellular membranes. |
| T172 |
440-537 |
Sentence |
denotes |
SARS-CoV is then internalized and penetrates early endosomes in a clathrin-dependent manner (62). |
| T173 |
538-675 |
Sentence |
denotes |
Viral binding to ACE2 appears to affect TNF-α activity, which in the presence of calmodulin inhibitors promotes ectodomain cleavage (63). |
| T174 |
676-1115 |
Sentence |
denotes |
In the case of SARS-CoV-2, it is possible this shedding is also mediated by TNF-α because 1 of the clinical features noted in patients with COVID-19 has been the presence of a cytokine storm with increased plasma concentrations of IL-2, IL-7, IL-10, granulocyte-colony stimulating factor (GCSF), interferon gamma-induced protein 10 (IP10), monocyte chemoattractant protein 1, macrophage inflammatory protein 1 alpha (MIP1A), and TNF-α (2). |
| T175 |
1116-1215 |
Sentence |
denotes |
It is also possible that ACE2 shedding may be mediated by other cytokines dysregulated in COVID-19. |
| T176 |
1216-1330 |
Sentence |
denotes |
This shedding contributes to the down-regulation of membrane-bound ACE2 observed in severe acute lung injury (64). |
| T177 |
1331-1485 |
Sentence |
denotes |
Ectodomain shedding increases the concentration of plasma ACE2, which remains catalytically active, although the function of soluble ACE2 remains unclear. |
| T178 |
1486-1699 |
Sentence |
denotes |
In patients with advanced heart failure, plasma ACE2 activity is increased in direct proportion with worsening clinical status and reduction in ejection fraction and correlates with adverse clinical outcomes (65). |
| T179 |
1700-2141 |
Sentence |
denotes |
Because down-regulation of bound ACE2 is observed in severe acute lung injury (65) and after myocardial infarction (46), and concentrations of soluble ACE2 appear to correlate with clinical outcomes of patients with heart failure (30), it is possible to suggest that concentrations of soluble ACE2 may correlate to the extent of tissue damage sustained and may correlate to the degree by which systemic inflammatory pathways are upregulated. |
| T180 |
2142-2225 |
Sentence |
denotes |
There is some evidence to suggest soluble ACE2 is able to regulate systemic Ang II. |
| T181 |
2226-2379 |
Sentence |
denotes |
Clinical trials have shown rhACE2 could convert systemic Ang II to Ang 1-7 (57,58) and play some pathological, compensatory, or counter regulatory roles. |
