LitCovid-sentences  

PMC:7161517 / 25809-30611 JSONTXT 12 Projects

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Id Subject Object Predicate Lexical cue
T157 0-19 Sentence denotes ACE2 and SARS-CoV-2
T158 20-203 Sentence denotes SARS-CoV, which emerged in the Guangdong province, China, and SARS-CoV-2, which emerged in Wuhan, China are closely related beta-coronaviruses whose affected receptor is ACE2 (1,3,4).
T159 204-359 Sentence denotes At this time, it is unknown if the approximate 76% sequence similarity between these strains of viruses translates into similar biological properties (14).
T160 360-488 Sentence denotes Recent studies have confirmed COVID-19 exploits ACE2 for entry and thus may target a similar spectrum of cells as SARS-CoV (14).
T161 489-548 Sentence denotes SARS-CoV-2 binds to ACE2 via its spike (S) protein (13,14).
T162 549-653 Sentence denotes The surface unit S1, of the S protein binds to ACE2, which facilitates viral attachment to target cells.
T163 654-908 Sentence denotes Following receptor binding, the virus must gain access to host cytosol, which is accomplished by acid-dependent proteolytic cleavage of the S protein by cellular serine protease TMPRSS2, which is similar to S protein priming in SARS-CoV (14) (Figure 2 ).
T164 909-969 Sentence denotes Figure 2 Proposed Mechanism of Entry for SARS-CoV-2 Via ACE2
T165 970-1085 Sentence denotes Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the catalytic site of ACE2 via its S protein.
T166 1086-1320 Sentence denotes To gain access to the host cytosol, the S protein undergoes acid dependent proteolytic cleavage by ACE2, tumor necrosis factor (TNF)-α, transmembrane protease serine 2 (TMPRRS2), which results in the formation of an S1 and S2 subunit.
T167 1321-1434 Sentence denotes S2 fusion peptide inserts into the membrane, which allows for clatherin-dependent endocytosis of ACE2-SARS-CoV-2.
T168 1435-1531 Sentence denotes Viral binding stimulates TNF-α and calmodulin inhibitors to promote ectodomain cleavage of ACE2.
T169 1532-1613 Sentence denotes ADAM 17 = disintegrin and metalloprotease 17; other abbreviations as in Figure 1.
T170 1614-1928 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 1929-2053 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 2054-2151 Sentence denotes SARS-CoV is then internalized and penetrates early endosomes in a clathrin-dependent manner (62).
T173 2152-2289 Sentence denotes Viral binding to ACE2 appears to affect TNF-α activity, which in the presence of calmodulin inhibitors promotes ectodomain cleavage (63).
T174 2290-2729 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 2730-2829 Sentence denotes It is also possible that ACE2 shedding may be mediated by other cytokines dysregulated in COVID-19.
T176 2830-2944 Sentence denotes This shedding contributes to the down-regulation of membrane-bound ACE2 observed in severe acute lung injury (64).
T177 2945-3099 Sentence denotes Ectodomain shedding increases the concentration of plasma ACE2, which remains catalytically active, although the function of soluble ACE2 remains unclear.
T178 3100-3313 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 3314-3755 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 3756-3839 Sentence denotes There is some evidence to suggest soluble ACE2 is able to regulate systemic Ang II.
T181 3840-3993 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.
T182 3994-4330 Sentence denotes If SARS-CoV-2 does induce ACE2 ectodomain shedding, which results in the reduction of ACE2 entry sites on the infected cell, it is possible that following transcription S proteins fuse directly at the host cell membrane and directly promote infection of neighboring cells, which results in the formation of multinucleated syncytia (66).
T183 4331-4469 Sentence denotes Formation of multinucleated cells would allow the virus to spread without being detected or neutralized by virus-specific antibodies (66).
T184 4470-4647 Sentence denotes Otherwise, following replication and transcription, complete virion assembly in the Golgi would result in transportation of the virus in vesicles and release by exocytosis (66).
T185 4648-4802 Sentence denotes In the setting of full virion assembly and exocytosis, it is unclear if ACE2 ectodomain shedding would be favorable for further propagation and infection.