Evidence map›Paper›PMID 28034743›Full record

ArticleAntiviral research2017

Discovery of host-targeted covalent inhibitors of dengue virus.

Mélissanne de Wispelaere, Margot Carocci, Yanke Liang, Qingsong Liu, Eileen Sun, Michael L Vetter, Jinhua Wang, Nathanael S Gray, Priscilla L Yang

Abstract read
In one paragraph

Article in Antiviral research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Covalent Antiviral Agents.Advances in experimental medicine and biology · 2021
    Review
  4. Potential for Protein Kinase Pharmacological Regulation inInternational journal of molecular sciences · 2020
    Review
  5. Gut Microbiome Critically Impacts PCB-induced Changes in Metabolic Fingerprints and the Hepatic Transcriptome in Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2020
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
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

9 authors.

Mélissanne de WispelaereDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Margot CarocciDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Yanke LiangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Qingsong LiuDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Eileen SunDepartment of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA 02138, USA.
Michael L VetterDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Jinhua WangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Nathanael S GrayDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Priscilla L YangDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: priscilla_yang@hms.harvard.edu.

Funding

Treatments for Nipah Virus InfectionU54AI057159 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WHELAN, SEAN PJ · 2003 to 2013
$113.7M
INFECTIOUS DISEASE AND BASIC MICROBIOLOGICAL MECHANISMST32AI007061 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Marcia B Goldberg · 1985 to 2026
$12.1M
Validation of Src kinases as Anti-Dengue Viral TargetsR01AI076442 · NIAID · HARVARD MEDICAL SCHOOL · PI YANG, PRISCILLA LI-NING · 2008 to 2012
$2.1M
NIAID NIH HHS R01 AI076442NIAID NIH HHS T32 AI007061NIAID NIH HHS U54 AI057159
6 · The paper itself

Abstract

We report here on an approach targeting the host reactive cysteinome to identify inhibitors of host factors required for the infectious cycle of Flaviviruses and other viruses. We used two parallel cellular phenotypic screens to identify a series of covalent inhibitors, exemplified by QL-XII-47, that are active against dengue virus. We show that the compounds effectively block viral protein expression and that this inhibition is associated with repression of downstream processes of the infectious cycle, and thus significantly contributes to the potent antiviral activity of these compounds. We demonstrate that QL-XII-47's antiviral activity requires selective, covalent modification of a host target by showing that the compound's antiviral activity is recapitulated when cells are preincubated with QL-XII-47 and then washed prior to viral infection and by showing that QL-XII-47R, a non-reactive analog, lacks antiviral activity at concentrations more than 20-fold higher than QL-XII-47's IC

Indexed as

Drug DiscoveryAntiviral AgentsDengueDengue VirusFlavivirusHepacivirusHost-Pathogen InteractionsHumansVirus ReplicationWest Nile virusZika VirusAntiviral Agents

Identifiers

PMID28034743
PMCPMC5373925

What OpenQuestion holds

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Read underepoch 390

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.