Evidence map›Paper›PMID 12767995›Full record

ArticleJournal of virology2003

Specific inhibition of bovine viral diarrhea virus replicase.

Jin-Hua Sun, Julie A Lemm, Donald R O'Boyle, Jason Racela, Richard Colonno, Min Gao

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
5.1field-weighted citation impact, top 5% 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

14 citing papers in PubMed, 47 citations in OpenAlex.

  1. Trial
  2. Molecules (Basel, Switzerland) · 2024
    Review
  3. Article
  4. Article
  5. Article
  6. Article
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  8. Review
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  10. Review
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  12. Article
  13. Antivirals and antiviral strategies.Nature reviews. Microbiology · 2004
    Review
  14. 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

6 authors at 1 institution in 1 country.

Jin-Hua SunDepartment of Virology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA.
Julie A Lemm
Donald R O'Boyle
Jason Racela
Richard Colonno
Min Gao
Bristol-Myers Squibb (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Compound-1453 was identified and characterized as a specific inhibitor of bovine viral diarrhea virus (BVDV). The concentration of compound-1453 which results in 50% protection from virus-induced cytopathic effect is approximately 2.2 microM, with a therapeutic index of 60, and it is not active against a panel of RNA and DNA viruses. A time-of-addition experiment suggested that compound-1453 targets a stage of the viral life cycle after viral entry. To determine the target of compound-1453, resistant virus was generated. Resistant variants grew efficiently in the presence or absence of 33 micro M compound-1453 and exhibited replication efficiency in the presence of compound-1453 approximately 1,000-fold higher than that of the wild-type (wt) virus. Functional mapping and sequence analysis of resistant cDNAs revealed a single amino acid substitution (Glu to Gly) at residue 291 in the NS5B polymerase in all eight independently generated cDNA clones. Recombinant virus containing this single mutation retained the resistance phenotype and a replication efficiency similar to that of the original isolated resistant virus. Since compound-1453 did not inhibit BVDV polymerase activity in vitro (50% inhibitory concentration > 300 microM), we developed a membrane-based assay that consisted of a BVDV RNA replicase complex isolated from virus-infected cells. Compound-1453 inhibited the activity of the wt, but not the drug-resistant, replicase in the membrane assay at concentrations similar to those observed in the viral infection assay. This work presents a novel inhibitor of a viral RNA-dependent RNA replicase.

Indexed as

Amino Acid SequenceAnimalsAntiviral AgentsBenzimidazolesCattleCell LineDiarrhea Viruses, Bovine ViralDrug Resistance, ViralEnzyme InhibitorsMicrobial Sensitivity TestsMutationRNA-Dependent RNA PolymeraseRNA, ViralUreaViral Nonstructural ProteinsVirus ReplicationAntiviral AgentsBenzimidazolescompound-1453Enzyme InhibitorsRNA-Dependent RNA PolymeraseRNA, ViralUreaViral Nonstructural Proteins

Identifiers

PMID12767995
PMCPMC156199
OpenAlexW2096881171

What OpenQuestion holds

Textmetadata
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.