Evidence map›Paper›PMID 29914957›Full record

ArticleAntimicrobial agents and chemotherapy2018

Extinction of Zika Virus and Usutu Virus by Lethal Mutagenesis Reveals Different Patterns of Sensitivity to Three Mutagenic Drugs.

Maria Rosaria Bassi, Raquel Navarro Sempere, Prashansa Meyn, Charlotta Polacek, Armando Arias

Open access · hybridAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

23 citing papers in PubMed, 38 citations in OpenAlex.

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  15. Article
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  17. Synergistic lethal mutagenesis of hepatitis C virus.Antimicrobial agents and chemotherapy · 2019
    Article
  18. Review
  19. Article
  20. 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

5 authors at 2 institutions in 1 country.

Maria Rosaria Bassi *Technical University of Denmark, National Veterinary Institute (DTU Vet), Kemitorvet, Lyngby, Denmark.
Raquel Navarro Sempere *Technical University of Denmark, National Veterinary Institute (DTU Vet), Kemitorvet, Lyngby, Denmark.
Prashansa MeynTechnical University of Denmark, National Veterinary Institute (DTU Vet), Kemitorvet, Lyngby, Denmark.
Charlotta PolacekStatens Serum Institut, Copenhagen, Denmark.
Armando AriasTechnical University of Denmark, National Veterinary Institute (DTU Vet), Kemitorvet, Lyngby, Denmark arae@vet.dtu.dk.ORCID 0000-0002-4138-4608
Technical University of Denmark · DKStatens Serum Institut · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Flaviviruses constitute an increasing source of public health concern, with growing numbers of pathogens causing disease and geographic spread to temperate climates. Despite a large body of evidence supporting mutagenesis as a conceivable antiviral strategy, there are currently no data on the sensitivity to increased mutagenesis for Zika virus (ZIKV) and Usutu virus (USUV), two emerging flaviviral threats. In this study, we demonstrate that both viruses are sensitive to three ribonucleosides, favipiravir, ribavirin, and 5-fluorouracil, that have shown mutagenic activity against other RNA viruses while remaining unaffected by a mutagenic deoxyribonucleoside. Serial cell culture passages of ZIKV in the presence of these compounds resulted in the rapid extinction of infectivity, suggesting elevated sensitivity to mutagenesis. USUV extinction was achieved when a 10-fold dilution was applied between every passage, but not in experiments involving undiluted virus, indicating an overall lower susceptibility than ZIKV. Although the two viruses are inhibited by the same three drugs, ZIKV is relatively more susceptive to serial passage in the presence of purine analogues (favipiravir and ribavirin), while USUV replication is suppressed more efficiently by 5-fluorouracil. These differences in sensitivity typically correlate with the increases in the mutation frequencies observed in each nucleoside treatment. These results are relevant to the development of efficient therapies based on lethal mutagenesis and support the rational selection of different mutagenic nucleosides for each pathogen. We will discuss the implications of these results to the fidelity of flavivirus replication and the design of antiviral therapies based on lethal mutagenesis.

Indexed as

AmidesAnimalsAntiviral AgentsCell LineChlorocebus aethiopsEpithelial CellsFlavivirusFluorouracilMutagenesisMutagensMutation RateNucleosidesPyrazinesRibavirinRibonucleosidesSerial PassageAmidesAntiviral AgentsfavipiravirFluorouracilMutagensNucleosidesPyrazinesRibavirinRibonucleosides5-fluorouracilerror thresholdfavipiravirflaviviruslethal mutagenesismutation frequencyribavirinUsutu virusZika virus

Identifiers

PMID29914957
PMCPMC6125542
OpenAlexW2808775917

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.