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Viruses. 2018 Aug 12;10(8). pii: E423. doi: 10.3390/v10080423.

A Systems Approach to Study Immuno- and Neuro-Modulatory Properties of Antiviral Agents.

Author information

1
Institute of Technology, University of Tartu, 50090 Tartu, Estonia. eva.zusinaite@ut.ee.
2
Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway. aleksandr.ianevski@helsinki.fi.
3
Institute of Technology, University of Tartu, 50090 Tartu, Estonia. dianka96-96@mail.ru.
4
Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland. minna.poranen@helsinki.fi.
5
Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway. magnar.bjoras@ntnu.no.
6
Department of Microbiology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway. magnar.bjoras@ntnu.no.
7
Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway. jan.afset@ntnu.no.
8
Institute of Technology, University of Tartu, 50090 Tartu, Estonia. tanel.tenson@ut.ee.
9
Institute Molecular Medicine Finland (FIMM), University of Helsinki, 00014 Helsinki, Finland. vidya.velagapudi@helsinki.fi.
10
Institute of Technology, University of Tartu, 50090 Tartu, Estonia. andres.merits@ut.ee.
11
Institute of Technology, University of Tartu, 50090 Tartu, Estonia. denis.kainov@helsinki.fi.
12
Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway. denis.kainov@helsinki.fi.

Abstract

There are dozens of approved, investigational and experimental antiviral agents. Many of these agents cause serious side effects, which can only be revealed after drug administration. Identification of the side effects prior to drug administration is challenging. Here we describe an ex vivo approach for studying immuno- and neuro-modulatory properties of antiviral agents, which may be associated with potential side effects of these therapeutics. The current approach combines drug toxicity/efficacy tests and transcriptomics, which is followed by mRNA, cytokine and metabolite profiling. We demonstrated the utility of this approach with several examples of antiviral agents. We also showed that the approach can utilize different immune stimuli and cell types. It can also include other omics techniques, such as genomics and epigenomics, to allow identification of individual markers associated with adverse reactions to antivirals with immuno- and neuro-modulatory properties.

KEYWORDS:

antiviral agent; drug side effect; drug target; innate immunity; precision medicine; systems biology; virus

PMID:
30103549
PMCID:
PMC6116047
DOI:
10.3390/v10080423
[Indexed for MEDLINE]
Free PMC Article

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