LitCovid-sentences  

PMC:7441788 / 7426-14473 JSONTXT 25 Projects

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Id Subject Object Predicate Lexical cue
T58 0-2 Sentence denotes 4.
T59 4-45 Sentence denotes Mechanisms of CQ/HCQ in treating COVID-19
T60 47-51 Sentence denotes 4.1.
T61 53-71 Sentence denotes Antiviral activity
T62 73-79 Sentence denotes 4.1.1.
T63 81-122 Sentence denotes Hindrance of receptor recognition process
T64 123-214 Sentence denotes The S protein of SARS-CoV-2 is cleaved by host proteases into two subunits, S1 and S2 [19].
T65 215-398 Sentence denotes The S1 subunit binds to the host cell surface receptor angiotensin-converting enzyme 2 (ACE2) for virus attachment, and the S2 subunit fuses the virus and the host cell membrane [19].
T66 399-787 Sentence denotes The investigation of the effect of CQ on ACE2 in VeroE6 cells showed that effective anti-SARS-CoV-2 concentrations of CQ had no significant effect on the synthesis and glycosylation of S protein on the surface of SARS-CoV, and although it had no significant effect on the cell surface expression of ACE2, CQ could destroy the glycosylation at the terminal glycosylation site of ACE2 [13].
T67 788-1061 Sentence denotes Therefore, the mechanism of anti-CoV activity of CQ/HCQ may be at least partly related to the impairment of terminal glycosylation of ACE2, which may result in reduced binding affinities between ACE2 and SARS CoV S protein, thereby blocking receptor recognition (Figure 1).
T68 1062-1071 Sentence denotes Figure 1.
T69 1072-1190 Sentence denotes Schematic representation of the possible mechanisms of CQ/HCQ against CoVs replication and modulating immune response.
T70 1191-1822 Sentence denotes CQ/HCQ may synergistically exert antiviral and immunomodulatory effects on COVID-19 through multiple mechanisms including hindering the receptor recognition process by influencing the affinity of ACE2 and S protein, and the affinity for sialic acid and ganglioside; inhibiting the membrane fusion process by suppressing endolysosome acidification; suppressing the p38 activation and affecting host defense machinery, and preventing MHC class II expression (block expression of CD154 on the surface of CD4 + T cell) and TLR signaling and reducing the production of cytokines through inhibiting the activation of T cells and B cells.
T71 1823-2173 Sentence denotes ACE2, angiotensin-converting enzyme 2; COVID-19, coronavirus disease 2019; CQ, chloroquine; HCQ, hydroxychloroquine; CoVs, coronaviruses; MAPK, mitogen-activated protein kinase; MHC-II, major histocompatibility complex class II; TLR, toll-like receptor; cGAS, cyclic GMP-AMP synthase; IFN, interferon; IL, interleukin; TNF-α, tumor necrosis factor-α.
T72 2174-2459 Sentence denotes In addition to protein membrane receptors, infection of host cells by HCoVs also relies on sialic acid-containing glycoproteins and gangliosides, which are used by a broad range of viruses as receptors, such as influenza [20] and HCoVs including SARS-CoV [21] and HCoV-OC43 [13,22,23].
T73 2460-2658 Sentence denotes A recent molecular structure analysis showed that SARS-CoV-2 not only uses ACE2 as a receptor, but also recognizes highly conserved gangliosides on the host cell surface through sialic acid [24,25].
T74 2659-2799 Sentence denotes CQ/HCQ binds sialic acids and gangliosides with high affinity, which can prevent the attachment of SARSCoV-2 S protein to gangliosides [25].
T75 2800-2907 Sentence denotes CQ had inhibitory effect on quinone reductase 2 (QR2) involved in the biosynthesis of sialic acids [26,27].
T76 2908-3059 Sentence denotes Hence, the mechanism of anti-CoV activity of CQ/HCQ may also be related to hindering the recognition process of sialic acid and ganglioside (Figure 1).
T77 3061-3067 Sentence denotes 4.1.2.
T78 3069-3112 Sentence denotes Interference of the membrane fusion process
T79 3113-3240 Sentence denotes CoVs are enveloped RNA viruses, and their cell entry processes involve a principal route of receptor-mediated endocytosis [28].
T80 3241-3405 Sentence denotes Membrane fusion takes place in the endosomal compartment after endocytosis, which needs additional triggers such as pH acidification or proteolytic activation [29].
T81 3406-3645 Sentence denotes Multiple cellular proteases, such as trypsin, furin, proprotein convertase (PC) family, cathepsins, transmembrane protease/serine (TMPRSS) proteases and elastase, are involved in S protein activation, which can induce membrane fusion [30].
T82 3646-3880 Sentence denotes Among them, cathepsin L, with anoptimal pH of 3.0 to 6.5, is most commonly associated with activation of a variety of CoV S proteins [30], such as SARS-CoV [19], MERS-CoV [31], HCoV-229E [32], and mouse hepatitis virus 2 (MHV-2) [33].
T83 3881-4043 Sentence denotes A recent study found that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, in which cathepsin L is critical for priming of SARS-CoV-2 S protein [24].
T84 4044-4393 Sentence denotes A study investigated the detailed mechanism of action of CQ/HCQ in inhibiting SARS-CoV-2 entry, and co-localization of SARS-CoV-2 with early endosomes (EEs) or endolysosomes (ELs) in VeroE6 cells, and the results showed that CQ/HCQ hampered the transport of SARS-CoV-2 from EEs to ELs, indicating that CQ/HCQ might inhibit endosomal maturation [17].
T85 4394-4657 Sentence denotes These studies revealed that the mechanism of anti-CoV activity of CQ/HCQ may involve the inhibition of the endosome acidification process, which might inactivate lysosomal proteases, thus interfering with the fusion of virus and host membranes [34,35] (Figure 1).
T86 4659-4665 Sentence denotes 4.1.3.
T87 4667-4727 Sentence denotes Effects on cell signaling pathway and host defense machinery
T88 4728-4904 Sentence denotes The mitogen-activated protein kinase (MAPK) pathway transmits signals from the cell surface to the nucleus involved in the infection of CoVs such as MHV [36] and SARS-CoV [37].
T89 4905-5044 Sentence denotes CQ could inhibit HCoV-229E replication in human embryonic lung epithelial cells (L132) through suppressing the activation of p38 MAPK [38].
T90 5045-5210 Sentence denotes Moreover, HCQ could markedly induce the production of cellular reactive oxygen species (ROS), which play an important role in the activation of innate immunity [39].
T91 5211-5368 Sentence denotes HCQ also could trigger the host defense mechanism through the mitochondrial antiviral signaling (MAVS) pathway, resulting in anti-dengue virus activity [39].
T92 5369-5529 Sentence denotes Therefore, CQ/HCQ may also exert their antiviral activity by suppressing the activation of p38 MAPK pathway and affecting the host defense machinery (Figure 1).
T93 5531-5535 Sentence denotes 4.2.
T94 5537-5599 Sentence denotes Inhibitory effect on T cell activation and cytokine production
T95 5600-5702 Sentence denotes CQ/HCQ regulate the release of various pro-inflammatory factors, which are important immunomodulators.
T96 5703-5888 Sentence denotes Intracellular alkalinization by CQ/HCQ inhibits lysosomal activity, preventing antigen processing, major histocompatibility complex (MHC) class II expression and immune activation [40].
T97 5889-5999 Sentence denotes This process can inhibit T cell activation and block expression of CD154 on the surface of CD4 + T cells [41].
T98 6000-6132 Sentence denotes CQ also reduces cytokines such as interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α) produced by T cells and B cells [42].
T99 6133-6323 Sentence denotes At the same time, changes of endosomal pH can interfere with Toll-like receptor (TLR) signaling, such as TLR7 and TLR9 processing, inhibiting the activation and production of cytokines [43].
T100 6324-6475 Sentence denotes CQ/HCQ also weaken the cyclic GMP-AMP (cGAMP) synthase (cGAS) activity by inhibiting cytosolic DNA, thereby reducing type I interferon production [44].
T101 6476-6624 Sentence denotes In vitro, CQ/HCQ can also inhibit phospholipase A2, altering the metabolism of arachidonic acid, and reducing the production of prostaglandins [45].
T102 6625-6920 Sentence denotes Some clinical studies have found that high concentrations of cytokines and pro-inflammatory factors such as IL-6 and IL-10 are elevated in the plasma of critically ill patients infected with SARS-CoV-2 [46,47], suggesting that cytokine release syndrome (CRS) is associated with disease severity.
T103 6921-7047 Sentence denotes In the aspect of immune response, HCQ/CQ therefore are likely to inhibit CRS, delaying the progression of COVID-19 (Figure 1).