PMC:7441788 / 7499-10485 JSONTXT 22 Projects

Annnotations TAB TSV DIC JSON TextAE-old TextAE

Id Subject Object Predicate Lexical cue
T62 0-6 Sentence denotes 4.1.1.
T63 8-49 Sentence denotes Hindrance of receptor recognition process
T64 50-141 Sentence denotes The S protein of SARS-CoV-2 is cleaved by host proteases into two subunits, S1 and S2 [19].
T65 142-325 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 326-714 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 715-988 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 989-998 Sentence denotes Figure 1.
T69 999-1117 Sentence denotes Schematic representation of the possible mechanisms of CQ/HCQ against CoVs replication and modulating immune response.
T70 1118-1749 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 1750-2100 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 2101-2386 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 2387-2585 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 2586-2726 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 2727-2834 Sentence denotes CQ had inhibitory effect on quinone reductase 2 (QR2) involved in the biosynthesis of sialic acids [26,27].
T76 2835-2986 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).