LitCovid-sentences  

PMC:7408073 / 3877-13772 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T20 0-2 Sentence denotes 2.
T21 3-51 Sentence denotes ACE2-mediated SARS-CoV and SARS-CoV-2 Infections
T22 52-215 Sentence denotes Angiotensin-converting enzyme 2 (ACE2) was identified as a receptor for the spike (S) protein of SARS-CoV, finally facilitating viral entry into target cells [13].
T23 216-409 Sentence denotes ACE2 is abundantly expressed in airway epithelial cells and vascular endothelial cells, and it is believed to play a crucial role in the mechanism of acute lung injury induced by SARS-CoV [14].
T24 410-663 Sentence denotes The ability of spike-Fc protein treatment (3h) to downregulate ACE2 protein expression has been shown in an in vitro system (cell lines) and also in vivo in lung cells of mice [14,15], suggesting that ACE2 pathway may be down-modulated during infection.
T25 664-806 Sentence denotes However, ACE2 is constitutively expressed and released from the apical cell surface of human airway epithelia into airway surface liquid [16].
T26 807-1048 Sentence denotes Of note, its surface down-modulation upon spike protein challenge has been shown to be due to ACE2 shedding mediated by activation of extracellular ADAM17/TACE metalloprotease, which concomitantly induces shedding/production of TNFα [17,18].
T27 1049-1280 Sentence denotes Interestingly, ACE2 shedding is enhanced not only by binding with spike protein [17,18], but also by IL-1β and TNFα inflammatory cytokines [16], cytokines that are secreted at relatively high concentration in COVID-19 patients [2].
T28 1281-1565 Sentence denotes Moreover, soluble (s)ACE2 (induced or not by virus binding) released from human airway epithelia has been demonstrated to retain both its enzymatic activity and its binding ability for spike viral protein, finally reducing spike protein-mediated viral entry into target cells [16,17].
T29 1566-1730 Sentence denotes Therefore, the interaction of ACE2 with spike protein of SARS-CoV induces a cellular “protective” ACE2 shedding feedback response that initially limits viral entry.
T30 1731-1918 Sentence denotes Nevertheless, ADAM17/TACE-mediated ACE2 shedding or ACE2 enzymatic activity have been shown to intriguingly correlate positively with viral infection and disease complications [17,19,20].
T31 1919-2110 Sentence denotes In contrast, HNL63-CoV, which similarly binds to ACE2 through its spike protein, infects ACE2-bearing cells and mainly induces the common cold, leading to neither ACE2 shedding nor SARS [17].
T32 2111-2373 Sentence denotes Moreover, catalytically inactive forms of sACE2 can potently inhibit SARS-CoV infection [19,21], suggesting that events downstream of ACE2 shedding and/or its enzymatic activity may indirectly and subsequently favour viral infection and/or disease complications.
T33 2374-2645 Sentence denotes To this regard, sACE2 was also associated with myocardial pathological conditions [22] and cardiovascular complications including hypotension (known to enhance both renin and angiotensin I, the substrate of ACE/ACE2) and tachycardia were common in SARS-CoV patients [23].
T34 2646-2914 Sentence denotes Since spike protein has been shown to not inhibit ACE2 enzymatic activity that is retained by sACE2-spike protein complex [16,17,24] and, in general, sACE2 maintains its enzymatic activity, we cannot consider its higher circulating expression a mere disease biomarker.
T35 2915-3030 Sentence denotes Indeed, ACE2 shedding might repress its local function but it certainly enhances its circulating/systemic activity.
T36 3031-3359 Sentence denotes Interestingly, a recent integrative bioinformatics analysis shows that the gene expression of ACE2 in human bronchial cells infected with SARS-CoV is dramatically increased 24h after infection and remained at a high level for at least 2 days, suggesting that ACE2 may be involved in a positive feedback loop post-infection [25].
T37 3360-3662 Sentence denotes In the same report, it has been shown that ACE2 expression level in bronchial epithelium obtained by brushing from asthmatic and normal subjects was similar, suggesting that respiratory epithelial cells of healthy subjects and asthmatic patients have similar ability to bind to SARS-CoV-2 through ACE2.
T38 3663-3760 Sentence denotes Of note, ACE2 was also identified as the receptor for the novel spike protein of SARS-CoV-2 [13].
T39 3761-3924 Sentence denotes Although the role of ACE2 in the pathogenesis of SARS-CoV-2 and in inducing lung injury is still unknown, ACE2 behaves similarly to original SARS-CoV [13] (Box 1).
T40 3925-4111 Sentence denotes Box 1 The formation of spike-ACE2 protein complexes may initiate ACE2 systemic upregulation and may impair autologous antibody generation/recognition of anti-S1-Receptor Binding Domain.
T41 4112-4381 Sentence denotes The ACE2 interacts with the spike (S) protein, thereby serves as an entry receptor for SARS-CoVs, and this event is likely followed by conformational changes, cleavages and fusion of both spike viral and ACE2 proteins at the level of infected host cell plasma-membrane.
T42 4382-4567 Sentence denotes The SARS coronavirus surface spike glycoproteins consist of trimers formed by two spike, capsid-distal S1 and –proximal S2, protein regions, located on the outer envelope of the virion.
T43 4568-4824 Sentence denotes Spike proteins are clove-shaped trimers with three S1 heads and a trimeric S2 stalk that can bind the cellular ACE2 receptor when one S1 (possessing the receptor-binding domain) in the trimer adopts an “up” conformation (see Figure later in the Section 4).
T44 4825-5236 Sentence denotes The subsequent binding of ACE2 receptor to the spike glycoprotein triggers both the ADAM17-mediated ACE2 shedding and dissociation of S1 fragments by exogenous (furin-related or other) proteases from the spike trimer, which leads on one hand to one S1-ACE2 complex and two S1 free fragments, and on the other hand to fusion of S2 viral trimers and cellular membrane structures, finally producing cell infection.
T45 5237-5460 Sentence denotes The molecular mechanism model for SARS-CoV recognition and infection was well described by Song and collaborators [26] and a similar molecular interactions between SARS-CoV-2 and ACE2 has been recently hypothesized [27,28].
T46 5461-5653 Sentence denotes To complete the picture, a recent structural work reveals that the full-length human ACE2 is assembled as a dimer associated or not with amino acid transporter B0AT1, which sandwich ACE2 [28].
T47 5654-5791 Sentence denotes Binding of the spike protein trimer onto the ACE2 dimer suggests simultaneous binding of two spike protein trimers to an ACE2 dimer [28].
T48 5792-6060 Sentence denotes Each monomer of the ACE2 homodimer is composed of a membrane-proximal collectrin-like domain mediating homodimerization and necessary to position the molecule to the cell membrane, and of a membrane-distal ACE2 peptidase domain responsible for ACE2 substrate cleavage.
T49 6061-6247 Sentence denotes Collectrin-like domain consists of an extracellular ferredoxin-like fold domain, also called neck domain (residues 616 to 726), a single transmembrane helix and an intracellular segment.
T50 6248-6432 Sentence denotes The ACE2 cleavage site mediated by ADAM17/TACE has been predicted between amino acids 716 and 741 [16], which corresponds to neck-transmembrane boundary of ACE2 collectrin-like domain.
T51 6433-6665 Sentence denotes It is tempting to speculate that, after ACE2 shedding, S2 viral trimers may fuse with the residual ACE2 collectrin-like fragments (complexed or not with B0AT1 transporters) which are eventually exposed on the cell surface membranes.
T52 6666-6770 Sentence denotes A model for SARS-CoV’s internalization by target cells that was already proposed several years ago [29].
T53 6771-7016 Sentence denotes Then, when the virus is inside the cell, a second proteolytic cleavage mediated by endosomal proteases (such as TMPRSS2) in the S2 region of the spike-ACE2 fusion protein might be necessary for intracellular virus “release” and active infection.
T54 7017-7174 Sentence denotes Several S1-sACE2 complexes, free S1 fragments or sACE2 are likely released in bloodstream of COVID-19 infected patients by spike and ACE2 receptor cleavages.
T55 7175-7650 Sentence denotes As already mentioned, circulating sACE2 protein shedding independent on virus contact has been also described either spontaneously when ACE2 transcription is upregulated or upon cytokine activation; it is therefore likely that in the bloodstreams ACE2 proteins are available to bind to both free S1 fragments and SARS-CoV-2 particles, finally leading to more and more S1-sACE2 and SARS-CoV-2-sACE2 complexes bearing enzymatic active sACE2 (see Figure later in the Section 4).
T56 7651-7926 Sentence denotes Of note, SARS-CoV-2-sACE2 complexes, sequestrating sACE2, can drive part of the sACE2 systemic activity and concentrate it locally where the organs possess cells expressing ACE2 on their surface membrane, i.e., following the viral tropism (see Figure later in the Section 4).
T57 7927-8221 Sentence denotes Indeed, although the viral load in sputum of adult SARS-CoV patients was usually higher than 104 copies/mL, reports indicate that plasma viral RNA concentrations are low, usually lower than 190 copies/mL and lymphocytes have much higher RNA-copy concentrations of SARS-CoV RNA than plasma [30].
T58 8222-8367 Sentence denotes Very low RNA concentrations with no difference between patients with mild or severe symptoms were detected in plasma from COVID-19 patients [30].
T59 8368-8499 Sentence denotes The viral load in nasal swabs of asymptomatic and symptomatic COVID-19-positive subjects was also not significantly different [31].
T60 8500-8784 Sentence denotes Of interest, SARS-CoV infected pediatric patients have more than double the amount of plasma RNA copies/mL when compared to adult patients [30], suggesting a different viral tropism between adults and children (different cellular ACE2 expression possibly leading to Kawasaki disease).
T61 8785-8912 Sentence denotes Notably, free S1 fragments may have a decoy function for autologous/exogenous anti-S1-receptor binding domain (RBD) antibodies.
T62 8913-9143 Sentence denotes On the other hand, sACE2-S1 complexes masking S1-RBD might also impair either generation of autologous high affinity antibodies against S1-RBD or recognition/inactivation of S1-RBD on SARS-CoV-2 by autologous/exogenous antibodies.
T63 9144-9516 Sentence denotes Therefore, antibodies that do not compete with ACE2 for the binding to S1-RBD might be more effective in neutralizing SARS-CoV-2 [32,33], knowing that the number of spike proteins per virion is estimated to be around 70 and that every spike protein bears three S1 receptor binding domains, which are masked to autologous antibody recognition when in a “down” conformation.
T64 9517-9712 Sentence denotes These highly organized molecular features clearly demonstrate that the coronaviruses are armed with sophisticated infection machinery able to evade immune responses induced or not by vaccination.
T65 9713-9895 Sentence denotes Nevertheless, passive immunotherapy by means of convalescent plasma from COVID-19 recovered donors is a promising option for prevention and treatment of COVID-19 [32,33,34,35,36,37].