Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19.
Sci Rep
; 11(1): 2512, 2021 01 28.
Article
in English
| MEDLINE | ID: covidwho-1054059
ABSTRACT
Whenever some phenomenon can be represented as a graph or a network it seems pertinent to explore how much the mathematical properties of that network impact the phenomenon. In this study we explore the same philosophy in the context of immunology. Our objective was to assess the correlation of "size" (number of edges and minimum vertex cover) of the JAK/STAT network with treatment effect in rheumatoid arthritis (RA), phenotype of viral infection and effect of immunosuppressive agents on a system infected with the coronavirus. We extracted the JAK/STAT pathway from Kyoto Encyclopedia of Genes and Genomes (KEGG, hsa04630). The effects of the following drugs, and their combinations, commonly used in RA were tested methotrexate, prednisolone, rituximab, tocilizumab, tofacitinib and baricitinib. Following viral systems were also tested for their ability to evade the JAK/STAT pathway Measles, Influenza A, West Nile virus, Japanese B virus, Yellow Fever virus, respiratory syncytial virus, Kaposi's sarcoma virus, Hepatitis B and C virus, cytomegalovirus, Hendra and Nipah virus and Coronavirus. Good correlation of edges and minimum vertex cover with clinical efficacy were observed (for edge, rho = - 0.815, R2 = 0.676, p = 0.007, for vertex cover rho = - 0.793, R2 = 0.635, p = 0.011). In the viral systems both edges and vertex cover were associated with acuteness of viral infections. In the JAK/STAT system already infected with coronavirus, maximum reduction in size was achieved with baricitinib. To conclude, algebraic and combinatorial invariant of a network may explain its biological behaviour. At least theoretically, baricitinib may be an attractive target for treatment of coronavirus infection.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Arthritis, Rheumatoid
/
Virus Diseases
/
STAT Transcription Factors
/
Janus Kinases
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Sci Rep
Year:
2021
Document Type:
Article
Affiliation country:
S41598-021-82139-x
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