LitCovid-sentences  

PMC:7118659 / 15081-21905 JSONTXT 16 Projects

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Id Subject Object Predicate Lexical cue
T87 0-105 Sentence denotes Chloroquine has been shown to be capable of inhibiting the in vitro replication of several coronaviruses.
T88 106-234 Sentence denotes Recent publications support the hypothesis that chloroquine can improve the clinical outcome of patients infected by SARS-CoV-2.
T89 235-345 Sentence denotes The multiple molecular mechanisms by which chloroquine can achieve such results remain to be further explored.
T90 346-658 Sentence denotes Since SARS-CoV-2 was found a few days ago to utilise the same cell surface receptor ACE2 (expressed in lung, heart, kidney and intestine) as SARS-CoV-1 [85,86] (Table 1 ), it may be hypothesised that chloroquine also interferes with ACE2 receptor glycosylation thus preventing SARS-CoV-2 binding to target cells.
T91 659-826 Sentence denotes Wang and Cheng reported that SARS-CoV and MERS-CoV upregulate the expression of ACE2 in lung tissue, a process that could accelerate their replication and spread [85].
T92 827-1183 Sentence denotes Although the binding of SARS-CoV to sialic acids has not been reported so far (it is expected that Betacoronavirus adaptation to humans involves progressive loss of hemagglutinin-esterase lectin activity), if SARS-CoV-2 like other coronaviruses targets sialic acids on some cell subtypes, this interaction will be affected by chloroquine treatment [87,88].
T93 1184-1467 Sentence denotes Today, preliminary data indicate that chloroquine interferes with SARS-CoV-2 attempts to acidify the lysosomes and presumably inhibits cathepsins, which require a low pH for optimal cleavage of SARS-CoV-2 spike protein [89], a prerequisite to the formation of the autophagosome [49].
T94 1468-1632 Sentence denotes Obviously, it can be hypothesised that SARS-CoV-2 molecular crosstalk with its target cell can be altered by chloroquine through inhibition of kinases such as MAPK.
T95 1633-1759 Sentence denotes Chloroquine could also interfere with proteolytic processing of the M protein and alter virion assembly and budding (Fig. 1 ).
T96 1760-1932 Sentence denotes Finally, in COVID-19 disease this drug could act indirectly through reducing the production of pro-inflammatory cytokines and/or by activating anti-SARS-CoV-2 CD8+ T-cells.
T97 1933-2074 Sentence denotes Table 1 Human coronavirus (HCoV) receptors/co-receptors as possible targets for chloroquine-induced inhibition of the virus replication cycle
T98 2075-2154 Sentence denotes Coronavirus Receptora May also bind Replication cycle inhibited by chloroquineb
T99 2155-2171 Sentence denotes Alphacoronavirus
T100 2172-2214 Sentence denotes  HCoV-229E Aminopeptidase N (APN)/CD13 Yes
T101 2215-2266 Sentence denotes  HCoV-NL63 Angiotensin-converting enzyme 2 (ACE2) ?
T102 2267-2297 Sentence denotes Heparan sulfate proteoglycansc
T103 2298-2313 Sentence denotes Betacoronavirus
T104 2314-2450 Sentence denotes  HCoV-OC43 HLA class Id, IFN-inducible transmembrane (IFITM) proteins in endocytic vesiclese Sialic acid (O-acetylated sialic acid)f Yes
T105 2451-2562 Sentence denotes  SARS-CoV-1 Angiotensin-converting enzyme 2 (ACE2) DC-SIGN/CD209, DC-SIGNr, DC-SIGN-related lectin LSECting Yes
T106 2563-2627 Sentence denotes  HCoV-HKU1 HLA class Ih Sialic acid (O-acetylated sialic acid) ?
T107 2628-2678 Sentence denotes  MERS-CoV i Dipeptidyl peptidase 4 (DPP4)/CD26 Yes
T108 2679-2709 Sentence denotes  SARS-CoV-2 ACE2i Sialic acid?
T109 2710-2713 Sentence denotes Yes
T110 2714-2743 Sentence denotes HLA, human leukocyte antigen.
T111 2744-2778 Sentence denotes a Adapted from Graham et al. [91].
T112 2779-2876 Sentence denotes b Chloroquine could interfere with receptor (ACE2) glycosylation and/or sialic acid biosynthesis.
T113 2877-2913 Sentence denotes c According to Milewska et al. [92].
T114 2914-2942 Sentence denotes d According to Collins [93].
T115 2943-2975 Sentence denotes e According to Zhao et al. [94].
T116 2976-3010 Sentence denotes f According to Vlasak et al. [95].
T117 3011-3044 Sentence denotes g According to Huang et al. [96].
T118 3045-3077 Sentence denotes h According to Chan et al. [97].
T119 3078-3349 Sentence denotes i It is worth noting that different host cell proteases are required to activate the spike (S) protein for coronaviruses, such as SARS-CoV-1 S protein that requires activation by cathepsin L [89], or MERS-CoV that requires furin-mediated activation of the S protein [98].
T120 3350-3507 Sentence denotes Fig. 1 Schematic representation of the possible effects of chloroquine on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication cycle.
T121 3508-3770 Sentence denotes SARS-CoV2, like other human coronaviruses, harbours three envelope proteins, the spike (S) protein (180–220 kDa), the membrane (M) protein (25–35 kDa) and the envelope (E) protein (10–12 kDa), which are required for entry of infectious virions into target cells.
T122 3771-3910 Sentence denotes The virion also contains the nucleocapsid (N), capable of binding to viral genomic RNA, and nsp3, a key component of the replicase complex.
T123 3911-4035 Sentence denotes A subset of betacoronaviruses use a hemagglutinin-esterase (65 kDa) that binds sialic acids at the surface of glycoproteins.
T124 4036-4083 Sentence denotes The S glycoprotein determines the host tropism.
T125 4084-4201 Sentence denotes There is indication that SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) expressed on pneumocytes [85,99].
T126 4202-4474 Sentence denotes Binding to ACE2 is expected to trigger conformational changes in the S glycoprotein allowing cleavage by the transmembrane protease TMPRSS2 of the S protein and the release of S fragments into the cellular supernatant that inhibit virus neutralisation by antibodies [100].
T127 4475-4783 Sentence denotes The virus is then transported into the cell through the early and late endosomes where the host protease cathepsin L further cleaves the S protein at low pH, leading to fusion of the viral envelope and phospholipidic membrane of the endosomes resulting in release of the viral genome into the cell cytoplasm.
T128 4784-4951 Sentence denotes Replication then starts and the positive-strand viral genomic RNA is transcribed into a negative RNA strand that is used as a template for the synthesis of viral mRNA.
T129 4952-5058 Sentence denotes Synthesis of the negative RNA strand peaks earlier and falls faster than synthesis of the positive strand.
T130 5059-5151 Sentence denotes Infected cells contain between 10 and 100 times more positive strands than negative strands.
T131 5152-5443 Sentence denotes The ribosome machinery of the infected cells is diverted in favour of the virus, which then synthesises its non-structural proteins (NSPs) that assemble into the replicase-transcriptase complex to favour viral subgenomic mRNA synthesis (see the review by Fehr and Perlman for details [101]).
T132 5444-5587 Sentence denotes Following replication, the envelope proteins are translated and inserted into the endoplasmic reticulum and then move to the Golgi compartment.
T133 5588-5731 Sentence denotes Viral genomic RNA is packaged into the nucleocapsid and then envelope proteins are incorporated during the budding step to form mature virions.
T134 5732-5889 Sentence denotes The M protein, which localises to the trans-Golgi network, plays an essential role during viral assembly by interacting with the other proteins of the virus.
T135 5890-6022 Sentence denotes Following assembly, the newly formed viral particles are transported to the cell surface in vesicles and are released by exocytosis.
T136 6023-6151 Sentence denotes It is possible that chloroquine interferes with ACE2 receptor glycosylation, thus preventing SARS-CoV-2 binding to target cells.
T137 6152-6283 Sentence denotes Chloroquine could also possibly limit the biosynthesis of sialic acids that may be required for cell surface binding of SARS-CoV-2.
T138 6284-6438 Sentence denotes If binding of some viral particles is achieved, chloroquine may modulate the acidification of endosomes thereby inhibiting formation of the autophagosome.
T139 6439-6567 Sentence denotes Through reduction of cellular mitogen-activated protein (MAP) kinase activation, chloroquine may also inhibit virus replication.
T140 6568-6670 Sentence denotes Moreover, chloroquine could alter M protein maturation and interfere with virion assembly and budding.
T141 6671-6782 Sentence denotes With respect to the effect of chloroquine on the immune system, see the elegant review by Savarino et al. [11].
T142 6783-6824 Sentence denotes ERGIC, ER-Golgi intermediate compartment.