Genomics-guided targeting of stress granule proteins G3BP1/2 to inhibit SARS-CoV-2 propagation.
Int J Biol Macromol
; 190: 636-648, 2021 Nov 01.
Article
in English
| MEDLINE | ID: covidwho-1401500
ABSTRACT
SARS-CoV-2 nucleocapsid (N) protein undergoes RNA-induced phase separation (LLPS) and sequesters the host key stress granule (SG) proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and 2 (G3BP1 and G3BP2) to inhibit SG formation. This will allow viral packaging and propagation in host cells. Based on a genomic-guided meta-analysis, here we identify upstream regulatory elements modulating the expression of G3BP1 and G3BP2 (collectively called G3BP1/2). Using this strategy, we have identified FOXA1, YY1, SYK, E2F-1, and TGFBR2 as activators and SIN3A, SRF, and AKT-1 as repressors of G3BP1/2 genes. Panels of the activators and repressors were then used to identify drugs that change their gene expression signatures. Two drugs, imatinib, and decitabine have been identified as putative modulators of G3BP1/2 genes and their regulators, suggesting their role as COVID-19 mitigation agents. Molecular docking analysis suggests that both drugs bind to G3BP1/2 with a much higher affinity than the SARS-CoV-2 N protein. This study reports imatinib and decitabine as candidate drugs against N protein and G3BP1/2 protein.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA-Binding Proteins
/
DNA Helicases
/
RNA Helicases
/
Adaptor Proteins, Signal Transducing
/
Molecular Dynamics Simulation
/
Molecular Docking Simulation
/
Imatinib Mesylate
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RNA Recognition Motif Proteins
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Poly-ADP-Ribose Binding Proteins
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Decitabine
Type of study:
Reviews
Language:
English
Journal:
Int J Biol Macromol
Year:
2021
Document Type:
Article
Affiliation country:
J.ijbiomac.2021.09.018
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