LitCovid-sentences  

PMC:7464116 / 14326-21890 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T90 0-2 Sentence denotes 4.
T91 3-18 Sentence denotes Pathophysiology
T92 19-177 Sentence denotes To understand the pathophysiological mechanism of SARS-CoV-2, its genomic sequence was compared to the other two similar coronaviruses, SARS-CoV and MERS-CoV.
T93 178-289 Sentence denotes In fact, it emerged that SARS-CoV-2 has a sequence identity of 79% with SARS-CoV and 50% with MERS-CoV [37,40].
T94 290-538 Sentence denotes Upon analysis of certain proteins, such as the coronavirus main proteinase (3CLpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp), it was observed that the sequence identity value between SARS-CoV and SARS-CoV-2 is 96% [41].
T95 539-657 Sentence denotes Therefore, an analogy between the physiopathological mechanisms of SARS-CoV and SARS-CoV-2 has been hypothesized [42].
T96 658-790 Sentence denotes Many studies reported that SARS-CoV-2, like SARS-CoV, uses Angiotensin converting enzyme 2 (ACE-2) to enter target cells [43,44,45].
T97 791-1098 Sentence denotes ACE-2 is a carboxypeptidase expressed on the cell surface which cleaves Angiotensin I (Ang I) into Angiotensin 1–9 and Angiotensin II (Ang II) into Angiotensin 1–7, counteracting the vasoconstrictor, proliferative and fibrotic effects of Angiotensin II generated by Angiotensin converting enzyme (ACE) [46].
T98 1099-1264 Sentence denotes Single-cell RNA sequencing analysis demonstrated a wide distribution of ACE-2 in different tissues [12,47] and histochemical staining then confirmed these data [48].
T99 1265-1530 Sentence denotes However, since low levels of ACE-2 expression were found on several cells types [47], it was supposed that cellular interaction and internalization by SARS-CoV-2did not depend only on ACE-2, but depended also on other auxiliary cell membrane receptors and proteins.
T100 1531-1613 Sentence denotes In fact, it is recognized that ssRNA viruses tend to have multiple receptors [49].
T101 1614-1791 Sentence denotes Qi et al. analyzed the expression of ACE-2 on 119 cell types from 13 human tissues and the coexpression characteristics of the ssRNA human viral receptors and membrane proteins.
T102 1792-1918 Sentence denotes Pearson correlation analysis of gene expression matrices showed 94 genes were found to be significantly correlated with ACE-2.
T103 1919-2111 Sentence denotes Among these, the coding genes of the peptidases alanylaminopeptidase (ANPEP), glutamyl aminopeptidase (ENPEP) and dipeptidyl peptidase 4 (DPP 4) showed the highest correlation with ACE-2 [12].
T104 2112-2405 Sentence denotes While both ANPEP and DPP4 are already known as a target receptors for other coronaviruses (human coronavirus 229E, swine epidemic diarrhea virus, canine coronavirus, feline coronavirus, for ANPEP and MERS-CoV for DPP4), the relationship between ENPEP and viral infection is not yet known [12].
T105 2406-2536 Sentence denotes ENPEP is a member of the M1 family of endopeptidases which are mammalian type II integral membrane zinc-containing endopeptidases.
T106 2537-2767 Sentence denotes It is mainly expressed in the terminal ileum and in the renal cortex and plays a role in the catabolic pathway of the Renin-Angiotensin system (RAAS), in the regulation of blood pressure and in the formation of blood vessels [50].
T107 2768-2902 Sentence denotes While the observations of Qi et al. suggest ENPEP may be a coronavirus receptor, further investigation is needed to confirm this [12].
T108 2903-3015 Sentence denotes However, the low expression of ACE-2 on the cell surface could also be interpreted as a viral defense mechanism.
T109 3016-3188 Sentence denotes In the past, the down regulation of ACE-2 had been correlated with faster cell-cell spread of human coronaviruses [51] and with more severe clinical manifestations [52,53].
T110 3189-3378 Sentence denotes Guzzi et al., in a recent study, hypothesized that even for COVID-19 the down regulation of ACE-2 could be a mechanism induced by SARS-CoV-2 to obtain a faster intercellular diffusion [54].
T111 3379-3612 Sentence denotes Studies carried out to understand the effect of angiotensin receptor blocker (ARB) drugs in patients with COVID-19, have suggested mechanisms through which the upregulation of ACE-2 may be protective during SARS-CoV-2 infection [55].
T112 3613-3683 Sentence denotes ARBs, in fact, greatly increase the cellular expression of ACE-2 [56].
T113 3684-4022 Sentence denotes However, since SARS-CoV-2-ACE-2 interaction represents the first step of a chain of events, if the upregulation of ACE-2 is not followed by the increase of certain cell proteases essential for internalization and viral activation, it would only result in the sequestration of SARS-CoV-2 on the cell membrane limiting viral infection [35].
T114 4023-4154 Sentence denotes Furthermore, the metalloproteinase ADAM17 can act upon the membrane-bound ACE-2, leading to the release of a soluble form of ACE-2.
T115 4155-4335 Sentence denotes If the increased expression of ACE-2 correlates with an increase in soluble ACE-2, this might act as a decoy receptor for SARS-CoV-2 by limiting viral entry into target cells [35].
T116 4336-4533 Sentence denotes Upon analysis of the SARS-CoV-2-ACE-2 interaction, there was confirmation that this occurs through the spike glycoprotein expressed on the viral envelope, being the same for all coronaviruses [35].
T117 4534-4787 Sentence denotes The coronavirus spike protein is composed of an intracellular segment, a transmembrane segment and a large ectodomain formed by an S1 subunit for interaction with the target receptor and an S2 subunit for fusion between the viral and cell membrane [57].
T118 4788-4904 Sentence denotes Subunit S1 consists of four domains, one N terminal domain (NTD) and three C-terminal domains (CTD1, CTD2 and CTD3).
T119 4905-5049 Sentence denotes The cell receptor and the viral protein bind through the receptor-binding domain (RBD), located in the CTD1 domain in the case of SARS-CoV [58].
T120 5050-5264 Sentence denotes Experiments undertaken to investigate virus-receptor interaction with resolution at the atomic level showed that SARS-CoV and SARS-CoV-2 had a high sequence similarity (89.2%) and sequence identity (73.7%) [14,22].
T121 5265-5432 Sentence denotes However, a more targeted evaluation of SARS-CoV-2 RBD revealed peculiar characteristics that are probably responsible for the greater diffusion compared with SARS-CoV.
T122 5433-5547 Sentence denotes Wan et al. found that the SARS-CoV-2 RBD has a single mutation that improves its binding affinity with ACE-2 [59].
T123 5548-5762 Sentence denotes Heet al. have shown that the characteristics of SARS-CoV-2 RBD make the virus more soluble, therefore capable of binding ACE-2 more easily, but also more stable, therefore able to survive at high temperatures [42].
T124 5763-5880 Sentence denotes At the same time, the SARS-CoV-2 RBD has greater flexibility than the SARS-CoV RBD, especially near the binding site.
T125 5881-6075 Sentence denotes For this reason, SARS-CoV-2 is much more sensitive to temperature than SARS-CoV in terms of the RBD-ACE-2 bond and this would cause the decrease in infectivity with increasing temperatures [42].
T126 6076-6226 Sentence denotes The SARS-CoV RBD-ACE-2 binding induces conformational changes in the S2 subunit, such as to induce the fusion between the viral membrane and the cell.
T127 6227-6345 Sentence denotes A low pH and pH-dependent endosomal cysteine proteases called cathepsins facilitate endosomal cell entry of the virus.
T128 6346-6558 Sentence denotes Furthermore, the S protein is cleaved into the S1 and S2 subunits by the host transmembrane cell proteases [60], which are necessary for the entry of the virus through the cell surface non-endosomal pathway [61].
T129 6559-6718 Sentence denotes Hoffmann et al. have shown that in particular SARS-CoV-2 S protein depends on the cellular protease Transmembrane Serine Protease 2 (TMPRSS2) for priming [62].
T130 6719-6845 Sentence denotes Therefore, the coexpression of ACE-2 and TMPRSS2 is a determining factor for the entry of SARS-CoV-2 into the host cells [63].
T131 6846-6991 Sentence denotes After entering the cell and becoming activated, SARS-CoV-2 uses the endogenous transcription mechanism of the cells to replicate and spread [60].
T132 6992-7119 Sentence denotes Cells infected by SARS-CoV-2 can recruit and modulate immune cells through the secretion of chemokines or other cytokines [12].
T133 7120-7166 Sentence denotes The role of macrophages remains to be defined.
T134 7167-7332 Sentence denotes In fact, the interaction between macrophages and cells expressing ACE-2 is known, suggesting a primary role of macrophages as a sentinel during viral infection [12].
T135 7333-7442 Sentence denotes A recent study, however, has shown a down regulation of mitochondrial proteins that interact with SARS-CoV-2.
T136 7443-7564 Sentence denotes This mechanism could be interpreted as a process through which the virus prevents apoptosis induced by mitochondria [54].