| Id |
Subject |
Object |
Predicate |
Lexical cue |
| TextSentencer_T1 |
0-74 |
Sentence |
denotes |
Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. |
| TextSentencer_T2 |
75-293 |
Sentence |
denotes |
Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), lead global epidemics with high morbidity and mortality. |
| TextSentencer_T3 |
294-373 |
Sentence |
denotes |
However, there are currently no effective drugs targeting 2019-nCoV/SARS-CoV-2. |
| TextSentencer_T4 |
374-544 |
Sentence |
denotes |
Drug repurposing, representing as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. |
| TextSentencer_T5 |
545-821 |
Sentence |
denotes |
In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. |
| TextSentencer_T6 |
822-972 |
Sentence |
denotes |
Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%). |
| TextSentencer_T7 |
973-1176 |
Sentence |
denotes |
Specifically, the envelope and nucleocapsid proteins of 2019-nCoV/SARS-CoV-2 are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. |
| TextSentencer_T8 |
1177-1516 |
Sentence |
denotes |
Using network proximity analyses of drug targets and HCoV-host interactions in the human interactome, we prioritize 16 potential anti-HCoV repurposable drugs (e.g., melatonin, mercaptopurine, and sirolimus) that are further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. |
| TextSentencer_T9 |
1517-1843 |
Sentence |
denotes |
We further identify three potential drug combinations (e.g., sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the "Complementary Exposure" pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human interactome network. |
| TextSentencer_T10 |
1844-2031 |
Sentence |
denotes |
In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations targeting 2019-nCoV/SARS-CoV-2. |
