LitCovid-sentences  

PMC:7461420 / 19305-28812 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T192 0-47 Sentence denotes 2.2 Inhibitors targeting the cellular receptor
T193 48-166 Sentence denotes The genetic code of SARS‐CoV‐2 shares noticeable similarities with SARS‐CoV‐1, which caused the SARS epidemic in 2002.
T194 167-247 Sentence denotes 26 , 54 More importantly, both viruses have identical mechanisms of infection.
T195 248-430 Sentence denotes SARS‐CoV‐1 uses the host's ACE2 as a portal to infect cells, which has high expression in the vascular endothelium 55 and the lung, particularly in type 2 alveolar epithelial cells.
T196 431-498 Sentence denotes 56 SARS‐CoV‐2 shares 76% of its spike (S) protein with SARS‐CoV‐1.
T197 499-733 Sentence denotes Despite a few amino acid differences in its RBD compared to the SARS‐CoV‐1 S protein, the SARS‐CoV‐2 S protein binds to ACE2 with even greater affinity 27 offering an explanation for its greater virulence and preference for the lung.
T198 734-902 Sentence denotes ACE, a highly glycosylated type I integral membrane protein, is an essential component of the renin‐angiotensin (Ang) system, which controls blood pressure homeostasis.
T199 903-942 Sentence denotes Both ACE1 and ACE2 cleave Ang peptides.
T200 943-1090 Sentence denotes However, they differ markedly: ACE1 cuts and converts the inactive decapeptide Ang I into the octapeptide Ang II by removing the dipeptide His‐Leu.
T201 1091-1344 Sentence denotes This Ang II induces vaso‐ and bronchoconstriction, increased vascular permeability, inflammation, and fibrosis, thus promoting acute respiratory distress syndrome (ARDS) and lung failure in patients infected with SARS‐CoV‐1 or SARS‐CoV‐2 57 (Figure 5).
T202 1345-1476 Sentence denotes Therefore, ACE‐inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) could block the disease‐propagating effect of Ang II.
T203 1477-1491 Sentence denotes 58 , 59 , 60
T204 1492-1558 Sentence denotes Figure 5 The roles of ACE1 and 2 in the renin‐angiotensin system.
T205 1559-1690 Sentence denotes A, Chemical structures of angiotensin‐related peptides and B, Schematic diagram of roles of ACE1 and 2 in renin‐angiotensin system.
T206 1691-1901 Sentence denotes ACE, angiotensin‐converting enzyme [Color figure can be viewed at wileyonlinelibrary.com] ACE2, on the other hand, is a zinc‐containing metalloenzyme, and shares merely 42% of its amino acid sequence with ACE1.
T207 1902-2057 Sentence denotes 61 It cleaves only one amino acid residue (Leu or Phe) from Ang I and Ang II, respectively, generating Ang (1–9) and Ang (1–7) (a vasodilator) (Figure 5).
T208 2058-2148 Sentence denotes Thus, ACE2 has been considered a potential therapeutic target for cardiovascular diseases.
T209 2149-2415 Sentence denotes Virtual screening combined with a molecular docking approach targeting the ACE2 catalytic site with around 140 000 compounds led to the identification of inhibitor N‐(2‐aminoethyl)‐1 aziridine‐ethanamine (7; Figure 6) with an IC50 value of 57 µM and a K i of 459 µM.
T210 2416-2500 Sentence denotes However, no information about the cytotoxicity of this compound is available so far.
T211 2501-2503 Sentence denotes 62
T212 2504-2561 Sentence denotes Figure 6 Inhibitors for SARS‐CoV‐1 and 2 targeting ACE2.
T213 2562-2777 Sentence denotes ACE, angiotensin‐converting enzyme; SARS‐CoV, severe acute respiratory syndrome coronavirus Chloroquine (8; Figure 6) is a relatively safe, cheap, and effective medication for the treatment of malaria and amebiasis.
T214 2778-2793 Sentence denotes Savarino et al.
T215 2794-2829 Sentence denotes 63 reported its antiviral effects.
T216 2830-2970 Sentence denotes At a molecular level, it increases late endosomal and lysosomal pH, resulting in impaired liberation of virions from endosomes or lysosomes.
T217 2971-3061 Sentence denotes The virus is therefore unable to release its genetic material into the cell and replicate.
T218 3062-3252 Sentence denotes 64 , 65 Furthermore, they hypothesize that chloroquine might block the production of proinflammatory cytokines (such as IL‐6), thereby blocking the pathway that subsequently leads to ARDS.
T219 3253-3255 Sentence denotes 63
T220 3256-3343 Sentence denotes Chloroquine is reasonably active in vitro against SARS‐CoV‐1, MERS‐CoV, and SARS‐CoV‐2.
T221 3344-3418 Sentence denotes It was found to inhibit SARS‐CoV‐2 with an EC50 value of 5.47 µM in vitro.
T222 3419-3608 Sentence denotes 66 Antiviral activity against SARS‐CoV‐1 was reported with an IC50 of 8.8 μM in Vero cells, but it is unclear how this translates into activity in respiratory epithelial cells and in vivo.
T223 3609-3867 Sentence denotes 67 , 68 Mechanistic studies of chloroquine for SARS‐CoV‐1 infection revealed that it could also weaken the interaction between the RBD of SARS‐CoV‐1 and ACE2 by interfering with terminal glycosylation of ACE2, thereby reducing its affinity to SARS‐CoV‐1 S.
T224 3868-3870 Sentence denotes 69
T225 3871-4117 Sentence denotes During the SARS‐CoV‐2 pandemic, chloroquine has been recommended by Chinese, South Korean, and Italian health authorities for the experimental treatment of COVID‐19, 70 , 71 despite contraindications for patients with heart disease or diabetes.
T226 4118-4334 Sentence denotes 72 However, health experts and agencies like the US FDA and European Medicines Agency warned against broad uncontrolled use after reports of misuse of low‐quality versions of chloroquine phosphate intended for fish.
T227 4335-4427 Sentence denotes Hydroxychloroquine (9; Figure 6) is being studied as an experimental treatment for COVID‐19.
T228 4428-4494 Sentence denotes 73 However, the benefits of treatment with this drug are unclear.
T229 4495-4497 Sentence denotes 74
T230 4498-4588 Sentence denotes Hydroxychloroquine was found to inhibit SARS‐CoV‐2 with an EC50 value of 0.74 µM in vitro.
T231 4589-4671 Sentence denotes 66 Some studies imply synergistic effects of hydroxychloroquine and azithromycin.
T232 4672-4881 Sentence denotes Azithromycin is active in vitro against Zika and Ebola virus 75 , 76 and can be used to guard against life‐threatening bacterial superinfections when administered to patients suffering from viral infections.
T233 4882-5038 Sentence denotes 77 A small study that compared hydroxychloroquine monotherapy and combination treatment with azithromycin found a significant advantage of the combination.
T234 5039-5436 Sentence denotes While evaluating the efficacy of therapeutic intervention with hydroxychloroquine as monotherapy and its impact in combination with azithromycin, the number of patients testing negative in polymerase chain reaction (PCR) tests was substantially different in the two groups with 100% of patients cured (6 days post inclusion) in the combination arm of the study versus 57% in the monotherapy group.
T235 5437-5532 Sentence denotes At the same time, 12% of patients in the control group receiving only standard care were cured.
T236 5533-5541 Sentence denotes 78 , 79
T237 5542-5734 Sentence denotes The WHO declared on 18 March that chloroquine and its derivative hydroxychloroquine will be among the four medicines studied in the solidarity clinical trial 80 for the treatment of COVID‐19.
T238 5735-5861 Sentence denotes In April 2020, the US National Institutes of Health (NIH) also commenced a study with the drug for treating COVID‐19 patients.
T239 5862-5864 Sentence denotes 81
T240 5865-6111 Sentence denotes The recent clinical trial involving 96 032 patients with COVID‐19 concluded that it was unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or in combination with a macrolide such as azithromycin (or clarithromycin).
T241 6112-6223 Sentence denotes 82 The study actually reported decreased survival rates for patients treated with each of these drug regimens.
T242 6224-6322 Sentence denotes Additionally, patients had an increased risk of developing ventricular arrhythmia under treatment.
T243 6323-6609 Sentence denotes However, still more evidence is needed to adequately assess the drugs' risks or benefits for the treatment or prevention of COVID‐19 (it is important to note that chloroquine and hydroxychloroquine are still considered safe treatment options in certain autoimmune diseases and malaria).
T244 6610-6743 Sentence denotes Besides, the WHO announced the premature pause of its clinical trials using hydroxychloroquine as a safety precaution on 24 May 2020.
T245 6744-6873 Sentence denotes On a different note, it was found that ACE2 undergoes proteolytic shedding; releasing an enzymatic ectodomain during viral entry.
T246 6874-7009 Sentence denotes 83 A disintegrin and metalloproteinase (ADAM), also known as TNF‐α converting enzyme (TACE), assisted the shedding regulation of ACE2.
T247 7010-7068 Sentence denotes Inhibition of this enzyme led to reduced shedding of ACE2.
T248 7069-7172 Sentence denotes GW280264X (10; Figure 6) was found to be a specific inhibitor of ADAM‐induced shedding of ACE2 at 1 nM.
T249 7173-7309 Sentence denotes 84 Two TACE inhibitors, TAPI‐0 (11) and TAPI‐2 (12; Figure 6), reduced ACE2 shedding, with IC50 values of 100 and 200 nM, respectively.
T250 7310-7312 Sentence denotes 83
T251 7313-7408 Sentence denotes MLN‐4760 (13; Figure 6) inhibited the catalytic activity of ACE2 with an IC50 of around 440 pM.
T252 7409-7592 Sentence denotes 85 This is the most potent and selective small‐molecule inhibitor against soluble human ACE2 described to date, thus making it a very promising candidate for SARS‐CoV‐2 interference.
T253 7593-7668 Sentence denotes It binds to the active site zinc and emulates the transition state peptide.
T254 7669-7740 Sentence denotes However, no antiviral data for this compound is available at this time.
T255 7741-7900 Sentence denotes The interference of a virus‐host cell fusion, which is mediated by the viral S protein to its receptor ACE2 on host cells, may be a viable prevention strategy.
T256 7901-8052 Sentence denotes Umifenovir (14; brand name Arbidol), a broad spectrum antiviral drug used against influenza, prevents viral entry by inhibiting virus‐host cell fusion.
T257 8053-8144 Sentence denotes 86 It is currently being investigated in a clinical trial for the treatment of SARS‐CoV‐2.
T258 8145-8153 Sentence denotes 87 , 88
T259 8154-8250 Sentence denotes Do ACEis or ARBs amplify SARS‐CoV‐2 pathogenicity and aggravate the clinical course of COVID‐19?
T260 8251-8420 Sentence denotes After ACE2 was recognized as the SARS‐CoV‐2 receptor, 14 , 29 speculations emerged about potentially negative consequences of ACEi or ARB therapy in COVID‐19 patients.
T261 8421-8508 Sentence denotes This theory caused confusion in the public and alarmed patients taking these medicines.
T262 8509-8630 Sentence denotes One report said that the expression of ACE2 was increased in patients with heart disease compared to healthy individuals.
T263 8631-8792 Sentence denotes It was also insisted that ACE2 expression could be increased by taking ACEis and ARBs, 89 although there is no supporting report of this happening in the lungs.
T264 8793-9002 Sentence denotes In another report, it was suggested that patients suffering from high blood pressure receiving “ACE2‐increasing drugs” have a higher risk for severe COVID‐19, since ACEis and ARBs could elevate levels of ACE2.
T265 9003-9005 Sentence denotes 90
T266 9006-9234 Sentence denotes A joint declaration by the presidents of the HFSA/ACC/AHA on 17 March 2020, 91 followed by a similar statement of the European Medicines Agency, 92 clarified that there was no scientific basis for stopping ACEi or ARB therapy.
T267 9235-9330 Sentence denotes 93 , 94 , 95 This was in accordance with the editors of the New England Journal of Medicine.
T268 9331-9333 Sentence denotes 96
T269 9334-9504 Sentence denotes In case of SARS‐CoV, the experimental data showed that such medications may be beneficial rather than damaging, which led to a new therapeutic approach for lung diseases.
T270 9505-9507 Sentence denotes 97