Drug Repurposing for COVID-19 by Constructing a Comorbidity Network with Central Nervous System Disorders
Abstract
:1. Introduction
2. Results
2.1. Construction of the Comorbidity Network
2.2. Identification of the Drug–Target Module
2.3. Drug Repositioning for the Target Module
2.4. UCHL1 Served as a Potential Drug Target
2.5. Identification of Potential Drug Candidates Based on the UCHL1 Drug–Target Network
3. Discussion
4. Materials and Methods
4.1. Collection of Disease-Associated Proteins
4.2. Network Construction and Modular Analysis
4.3. Functional Enrichment Analysis
4.4. Screening of Drug–Response Modules
4.5. Weighted Drug–Target Network
4.6. Perturbation-Response-Scanning Analysis
4.7. RNA-Seq Data Analysis
4.8. Drug Annotation
4.9. Molecular Docking
4.10. Molecular Dynamics Simulations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug | ΔGDocking (kcal/mol) | Indication | MOA | Clinical Trial |
---|---|---|---|---|
pregnenolone | −7.7 | NA | dopamine release enhancer | Phase 2—ASD |
methysergide | −7.2 | vascular headache | serotonin receptor antagonist | |
flutamide | −6.5 | prostate cancer | androgen receptor antagonist | |
propantheline | −6 | antimuscarinic agent | acetylcholine receptor antagonist | |
zileuton | −5.9 | chronic asthma | lipoxygenase inhibitor | Phase1—Pneumonia |
benactyzine | −5.7 | depression and related anxiety | acetylcholine receptor antagonist | |
lidocaine | −5.4 | amide-based anesthetic | histamine receptor agonist | Phase3—COVID-19 |
pseudopelletierine | −4.9 | NA | anthelmintic | |
norepinephrine | −4.8 | vasovagal shock | adrenergic receptor agonist | |
BRD-K95482240 | −9.3 | NA | tubulin polymerization inhibitor | |
BRD-K62493605 | −8.4 | NA | dopamine receptor antagonist | |
BRD-K35708212 | −8.4 | NA | BCL inhibitor | |
BRD-K87426499 | −8.1 | NA | dopamine receptor antagonist | |
BRD-A26595446 | −8 | NA | cyclooxygenase inhibitor | |
BRD-K46267071 | −8 | NA | NA | |
BRD-K83151319 | −7.8 | NA | PI3K inhibitor | |
BRD-K33586157 | −7.6 | NA | cyclooxygenase inhibitor | |
BRD-K82857306 | −7.5 | NA | MEK inhibitor | |
BRD-K18587499 | −7.3 | NA | histamine receptor antagonist | |
BRD-K48924007 | −6.8 | NA | dopamine receptor antagonist | |
BRD-K00859168 | −6.5 | NA | topoisomerase inhibitor | |
BRD-K99311057 | −6.2 | NA | cyclooxygenase inhibitor | |
BRD-K04188046 | −5.8 | NA | adrenergic receptor antagonist | |
BRD-A96272097 | −5.2 | NA | dopamine receptor antagonist |
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Qian, J.; Yang, B.; Wang, S.; Yuan, S.; Zhu, W.; Zhou, Z.; Zhang, Y.; Hu, G. Drug Repurposing for COVID-19 by Constructing a Comorbidity Network with Central Nervous System Disorders. Int. J. Mol. Sci. 2024, 25, 8917. https://doi.org/10.3390/ijms25168917
Qian J, Yang B, Wang S, Yuan S, Zhu W, Zhou Z, Zhang Y, Hu G. Drug Repurposing for COVID-19 by Constructing a Comorbidity Network with Central Nervous System Disorders. International Journal of Molecular Sciences. 2024; 25(16):8917. https://doi.org/10.3390/ijms25168917
Chicago/Turabian StyleQian, Jing, Bin Yang, Shuo Wang, Su Yuan, Wenjing Zhu, Ziyun Zhou, Yujuan Zhang, and Guang Hu. 2024. "Drug Repurposing for COVID-19 by Constructing a Comorbidity Network with Central Nervous System Disorders" International Journal of Molecular Sciences 25, no. 16: 8917. https://doi.org/10.3390/ijms25168917