LitCovid-sentences  

PMC:7073332 / 14737-17989 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T91 0-40 Sentence denotes Network-based drug repurposing for HCoVs
T92 41-319 Sentence denotes The basis for the proposed network-based drug repurposing methodologies rests on the notions that the proteins that associate with and functionally govern viral infection are localized in the corresponding subnetwork (Fig. 1a) within the comprehensive human interactome network.
T93 320-620 Sentence denotes For a drug with multiple targets to be effective against an HCoV, its target proteins should be within or in the immediate vicinity of the corresponding subnetwork in the human protein–protein interactome (Fig. 1), as we demonstrated in multiple diseases13,22,23,28 using this network-based strategy.
T94 621-788 Sentence denotes We used a state-of-the-art network proximity measure to quantify the relationship between HCoV-specific subnetwork (Fig. 3a) and drug targets in the human interactome.
T95 789-941 Sentence denotes We constructed a drug–target network by assembling target information for more than 2000 FDA-approved or experimental drugs (see Materials and methods).
T96 942-1407 Sentence denotes To improve the quality and completeness of the human protein interactome network, we integrated PPIs with five types of experimental data: (1) binary PPIs from 3D protein structures; (2) binary PPIs from unbiased high-throughput yeast-two-hybrid assays; (3) experimentally identified kinase-substrate interactions; (4) signaling networks derived from experimental data; and (5) literature-derived PPIs with various experimental evidence (see Materials and methods).
T97 1408-1645 Sentence denotes We used a Z-score (Z) measure and permutation test to reduce the study bias in network proximity analyses (including hub nodes in the human interactome network by literature-derived PPI data bias) as described in our recent studies13,28.
T98 1646-1831 Sentence denotes In total, we computationally identified 135 drugs that were associated (Z < −1.5 and P < 0.05, permutation test) with the HCoV–host interactome (Fig. 4a, Supplementary Tables S4 and 5).
T99 1832-2071 Sentence denotes To validate bias of the pooled cellular proteins from six CoVs, we further calculated the network proximities of all the drugs for four CoVs with a large number of know host proteins, including SARS-CoV, MERS-CoV, IBV, and MHV, separately.
T100 2072-2205 Sentence denotes We found that the Z-scores showed consistency among the pooled 119 HCoV-associated proteins and other four individual CoVs (Fig. 4b).
T101 2206-2440 Sentence denotes The Pearson correlation coefficients of the proximities of all the drugs for the pooled HCoV are 0.926 vs. SARS-CoV (P < 0.001, t distribution), 0.503 vs. MERS-CoV (P < 0.001), 0.694 vs. IBV (P < 0.001), and 0.829 vs. MHV (P < 0.001).
T102 2441-2561 Sentence denotes These network proximity analyses offer putative repurposable candidates for potential prevention and treatment of HCoVs.
T103 2562-2600 Sentence denotes Fig. 4 A discovered drug-HCoV network.
T104 2601-2701 Sentence denotes a A subnetwork highlighting network-predicted drug-HCoV associations connecting 135 drugs and HCoVs.
T105 2702-2862 Sentence denotes From the 2938 drugs evaluated, 135 ones achieved significant proximities between drug targets and the HCoV-associated proteins in the human interactome network.
T106 2863-3076 Sentence denotes Drugs are colored by their first-level of the Anatomical Therapeutic Chemical (ATC) classification system code. b A heatmap highlighting network proximity values for SARS-CoV, MERS-CoV, IBV, and MHV, respectively.
T107 3077-3210 Sentence denotes Color key denotes network proximity (Z-score) between drug targets and the HCoV-associated proteins in the human interactome network.
T108 3211-3252 Sentence denotes P value was computed by permutation test.