Abstract | AIMS: MATERIALS AND METHODS: The differentially expressed genes (DEGs) were identified from microarray data repository of SARS-CoV patient blood. The repurposed drugs for COVID-19 were selected from available literature. Using DEGs and drugs, the protein- protein interaction (PPI) and chemo- protein interaction ( CPI) networks were constructed and combined to develop an interactome model of PPI- CPI network. The top-ranked sub-network with its hub-bottleneck nodes were evaluated with their functional annotations. KEY FINDINGS: A total of 120 DEGs and 65 drugs were identified. The PPI- CPI network (118 nodes and 293 edges) exhibited a top-ranked sub-network (35 nodes and 174 connectivities) with 12 hub-bottleneck nodes having two drugs chloroquine and melatonin in association with 10 proteins corresponding to six upregulated and four downregulated genes. Two drugs interacted directly with the hub-bottleneck node i.e. matrix metallopeptidase 9 (MMP9), a host protein corresponding to its upregulated gene. MMP9 showed functional annotations associated with neutrophil mediated immunoinflammation. Moreover, literature survey revealed that angiotensin converting enzyme 2, a membrane receptor of SARS-CoV-2 virus, might have functional cooperativity with MMP9 and a possible interaction with both drugs. SIGNIFICANCE:
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Authors | Suvojit Hazra, Alok Ghosh Chaudhuri, Basant K Tiwary, Nilkanta Chakrabarti |
Journal | Life sciences
(Life Sci)
Vol. 257
Pg. 118096
(Sep 15 2020)
ISSN: 1879-0631 [Electronic] Netherlands |
PMID | 32679150
(Publication Type: Journal Article, Meta-Analysis)
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Copyright | Copyright © 2020 Elsevier Inc. All rights reserved. |
Chemical References |
- Antiviral Agents
- Chloroquine
- Metalloproteases
- Peptidyl-Dipeptidase A
- ACE2 protein, human
- Angiotensin-Converting Enzyme 2
- Matrix Metalloproteinase 9
- Melatonin
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Topics |
- Angiotensin-Converting Enzyme 2
- Antiviral Agents
(therapeutic use)
- Betacoronavirus
(drug effects, metabolism, pathogenicity)
- COVID-19
- Chloroquine
(pharmacology)
- Computational Biology
(methods)
- Coronavirus Infections
(drug therapy, metabolism, physiopathology)
- Humans
- Matrix Metalloproteinase 9
(metabolism)
- Melatonin
(pharmacology)
- Metalloproteases
(metabolism)
- Pandemics
- Peptidyl-Dipeptidase A
- Pneumonia, Viral
(metabolism, physiopathology)
- Protein Interaction Maps
(drug effects)
- Protein Transport
- SARS-CoV-2
- COVID-19 Drug Treatment
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