Evidence map›Paper›PMID 35420134›Full record

ArticleNucleic acids research2022

Guanine quadruplexes in the RNA genome of the tick-borne encephalitis virus: their role as a new antiviral target and in virus biology.

Jiří Holoubek, Klára Bednářová, Jan Haviernik, Ivana Huvarová, Zuzana Dvořáková, Jiří Černý, Martina Outlá, Jiří Salát, Eva Konkol'ová, Evzen Boura and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
9.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 39 citations in OpenAlex.

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  10. Tick-Borne Encephalitis (TBE): From Tick to Pathology.Journal of clinical medicine · 2023
    Review
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 1 country.

Jiří HoloubekVeterinary Research Institute, Emerging Viral Diseases, Brno CZ-62100, Czech Republic.
Klára BednářováDepartment of Biophysics of Nucleic Acids, Institute of Biophysics of the Czech Academy of Sciences, Brno CZ-61200, Czech Republic.
Jan HaviernikVeterinary Research Institute, Emerging Viral Diseases, Brno CZ-62100, Czech Republic.
Ivana HuvarováVeterinary Research Institute, Emerging Viral Diseases, Brno CZ-62100, Czech Republic.
Zuzana DvořákováDepartment of Biophysics of Nucleic Acids, Institute of Biophysics of the Czech Academy of Sciences, Brno CZ-61200, Czech Republic.
Jiří ČernýFaculty of Tropical Agrisciences, Czech University of Life Sciences Prague, CZ-16500 Prague, Czech Republic.
Martina OutláDepartment of Biophysical Chemistry and Molecular Oncology, Institute of Biophysics of the Czech Academy of Sciences, Brno CZ-61200, Czech Republic.
Jiří SalátVeterinary Research Institute, Emerging Viral Diseases, Brno CZ-62100, Czech Republic.
Eva Konkol'ováInstitute of Organic Chemistry and Biochemistry of the Czech Academy ofSciences, CZ-16000 Prague, Czech Republic.
Evzen BouraInstitute of Organic Chemistry and Biochemistry of the Czech Academy ofSciences, CZ-16000 Prague, Czech Republic.
Daniel RůžekVeterinary Research Institute, Emerging Viral Diseases, Brno CZ-62100, Czech Republic.ORCID 0000-0003-4655-2380
Michaela VorlíčkováDepartment of Biophysics of Nucleic Acids, Institute of Biophysics of the Czech Academy of Sciences, Brno CZ-61200, Czech Republic.ORCID 0000-0002-9153-5099
Luděk EyerVeterinary Research Institute, Emerging Viral Diseases, Brno CZ-62100, Czech Republic.
Daniel RenčiukDepartment of Biophysics of Nucleic Acids, Institute of Biophysics of the Czech Academy of Sciences, Brno CZ-61200, Czech Republic.ORCID 0000-0001-9293-7105
Czech Academy of Sciences, Institute of Biophysics · CZVeterinary Research Institute · CZMasaryk University · CZCzech Academy of Sciences · CZCzech University of Life Sciences Prague · CZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We have identified seven putative guanine quadruplexes (G4) in the RNA genome of tick-borne encephalitis virus (TBEV), a flavivirus causing thousands of human infections and numerous deaths every year. The formation of G4s was confirmed by biophysical methods on synthetic oligonucleotides derived from the predicted TBEV sequences. TBEV-5, located at the NS4b/NS5 boundary and conserved among all known flaviviruses, was tested along with its mutated variants for interactions with a panel of known G4 ligands, for the ability to affect RNA synthesis by the flaviviral RNA-dependent RNA polymerase (RdRp) and for effects on TBEV replication fitness in cells. G4-stabilizing TBEV-5 mutations strongly inhibited RdRp RNA synthesis and exhibited substantially reduced replication fitness, different plaque morphology and increased sensitivity to G4-binding ligands in cell-based systems. In contrast, strongly destabilizing TBEV-5 G4 mutations caused rapid reversion to the wild-type genotype. Our results suggest that there is a threshold of stability for G4 sequences in the TBEV genome, with any deviation resulting in either dramatic changes in viral phenotype or a rapid return to this optimal level of G4 stability. The data indicate that G4s are critical elements for efficient TBEV replication and are suitable targets to tackle TBEV infection.

Indexed as

Antiviral AgentsEncephalitis Viruses, Tick-BorneG-QuadruplexesEncephalitis, Tick-BorneHumansLigandsRNA-Dependent RNA PolymeraseRNA, ViralAntiviral AgentsLigandsRNA-Dependent RNA PolymeraseRNA, Viral

Identifiers

PMID35420134
PMCPMC9071444
OpenAlexW4220743107

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.