LitCovid-sentences  

PMC:7461420 / 14538-19303 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T150 0-22 Sentence denotes 2.1 Targeting the RBD
T151 23-135 Sentence denotes Structural investigations of the RBD‐ACE2 complex provided information about essential residues for viral entry.
T152 136-149 Sentence denotes Hsiang et al.
T153 150-289 Sentence denotes 35 reported a number of peptides that significantly blocked the interaction of the S protein with ACE2 with IC50 values as low as 1.88 nM.
T154 290-391 Sentence denotes Michael et al. found charged residues between positions 22 and 57 crucial for SARS‐CoV‐1 viral entry.
T155 392-525 Sentence denotes Based on this, they designed peptides P4 (IC50, 50 µM) and P5 (IC50, 6.0 µM) with significant inhibitory activity against SARS‐CoV‐1.
T156 526-794 Sentence denotes The antiviral activity was further improved when they introduced the glycine binding linkage of peptide P4 (residues 22–47) with an ACE2‐derived peptide (residues 351–357) against a SARS‐CoV‐1 pseudovirus with an IC50 of 100 nM and devoid of cytotoxicity up to 200 µM.
T157 795-882 Sentence denotes 36 It is worth highlighting that a similar strategy could work for the new SARS‐CoV‐2.
T158 883-1020 Sentence denotes The recently solved cryo‐EM structure of SARS‐CoV‐2 in complex with human ACE2 can provide a structural rationale for the peptide design.
T159 1021-1023 Sentence denotes 29
T160 1024-1197 Sentence denotes For viral entry, MERS‐CoV uses its spike protein (S) to interact with the host‐receptor DPP4, 37 , 38 , 39 also known as adenosine deaminase‐complexing protein‐2 or CD26.
T161 1198-1273 Sentence denotes 37 MERS‐CoV was also the first virus reported to use this particular path.
T162 1274-1422 Sentence denotes 35 , 37 DPP4 is a type II transmembrane glycoprotein, that forms homodimers on the cell surface, and it is involved in the cleavage of dipeptides.
T163 1423-1538 Sentence denotes 37 , 40 In humans, DPP4 is predominantly found on the bronchial epithelial and alveolar cells in the lower lungs.
T164 1539-1547 Sentence denotes 40 , 41
T165 1548-1698 Sentence denotes MERS‐4 and MERS‐27 are monoclonal antibodies targeting the RBD of MERS‐CoV S that were discovered in a nonimmune yeast‐display scFv library screening.
T166 1699-1830 Sentence denotes The more active MERS‐4 potently blocked the infection of DPP4‐expressing Huh‐7 cells with pseudotyped MERS‐CoV (IC50, 0.056 μg/mL).
T167 1831-1938 Sentence denotes It also prevented MERS‐CoV‐induced cytopathogenic effects in MERS‐infected Vero E6 cells (IC50, 0.5 μg/mL).
T168 1939-1941 Sentence denotes 42
T169 1942-2018 Sentence denotes A heptad repeat (HR) is a repeating structural pattern of seven amino acids.
T170 2019-2149 Sentence denotes A crucial membrane fusion framework of SARS‐CoV is the 6‐helix‐bundle (6‐HB) that is formed by HR1 and HR2 of the viral S protein.
T171 2150-2235 Sentence denotes Enfuvirtide (T‐20) is an FDA approved HR2 peptide and the first HIV fusion inhibitor.
T172 2236-2334 Sentence denotes It has opened up new avenues toward identifying and developing peptides as viral entry inhibitors.
T173 2335-2605 Sentence denotes Such molecules represent a promising strategy against enveloped viruses with class 1 fusion proteins such as Nipah virus, Hendra virus, Ebola virus, and other paramyxoviruses, simian immunodeficiency virus, feline immunodeficiency virus, and respiratory syncytial virus.
T174 2606-2805 Sentence denotes 43 , 44 , 45 , 46 The HR regions of SARS‐CoV‐1 and SARS‐CoV‐2 S protein share a high degree of conservation, and such fusion inhibitors have potential applications in preventing SARS‐CoV‐2 entry.
T175 2806-2889 Sentence denotes Small molecule entry inhibitors, on the other hand, are reported to target the RBD.
T176 2890-3066 Sentence denotes Compared to peptides, proteins, and biologics, small molecules have several advantages due to lower production costs, improved pharmacokinetics, stability, and dosage accuracy.
T177 3067-3254 Sentence denotes Sarafianos et al. identified the oxazole‐carboxamide derivative SSAA09E2 (1; Figure 4) as an entry inhibitor against SARS‐CoV‐1 by screening a chemical library composed of 3000 compounds.
T178 3255-3472 Sentence denotes 47 This inhibitor directly blocks ACE2 recognition by interfering with the RBD with an EC50 value of 3.1 µM and a 50% cytotoxic concentration (CC50) value of greater than 100 µM, not affecting ACE2 expression levels.
T179 3473-3475 Sentence denotes 48
T180 3476-3544 Sentence denotes Figure 4 Inhibitors targeting the receptor‐binding domain Xu et al.
T181 3545-3724 Sentence denotes 49 identified two small molecules, TGG (2; Figure 4) and luteolin (3; Figure 4), that can bind avidly to the SARS‐CoV‐1 S2 protein and inhibit its entry into Vero E6 cells (EC50:
T182 3725-3756 Sentence denotes 4.5 µM, 10.6 µM; respectively).
T183 3757-3908 Sentence denotes Compounds 2 and 3 showed cytotoxicity (CC50) of 1.08 and 0.155 mM, and the selectivity index (SI) values of 2 and 3 were 240.0 and 14.62, respectively.
T184 3909-4034 Sentence denotes Further studies regarding acute toxicity revealed that the 50% lethal doses of 2 and 3 were ~456 and 232 mg/kg, respectively.
T185 4035-4141 Sentence denotes These results indicate that these small molecules could be used at relatively high concentrations in mice.
T186 4142-4296 Sentence denotes 49 Quercetin (4; Figure 4), an analog of 3, also showed antiviral activity against SARS‐CoV‐1, with an EC50 value of 83.4 µM and a CC50 value of 3.32 mM.
T187 4297-4299 Sentence denotes 50
T188 4300-4414 Sentence denotes Ngai et al. reported ADS‐J1 (5; Figure 4) as a potential SARS‐CoV‐1 viral entry inhibitor with an EC50 of 3.89 µM.
T189 4415-4554 Sentence denotes Molecular docking studies predicted that 5 can bind into a deep pocket of the SARS‐CoV‐1 S HR region and block viral entry into host cells.
T190 4555-4756 Sentence denotes 51 Imatinib (6; Figure 4), an Abelson kinase inhibitor, could inhibit CoV S protein‐induced fusion with an EC50 value of 10 µM and showed no cytotoxic effects in Vero cells up to 100 µM concentration.
T191 4757-4765 Sentence denotes 52 , 53