Evidence map›Paper›PMID 17325220›Full record

ArticleAntimicrobial agents and chemotherapy2007

Selective phosphorylation of antiviral drugs by vaccinia virus thymidine kinase.

Mark N Prichard, Kathy A Keith, Mary P Johnson, Emma A Harden, Alexis McBrayer, Ming Luo, Shihong Qiu, Debasish Chattopadhyay, Xuesen Fan, Paul F Torrence and 1 more

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

16 citing papers in PubMed, 29 citations in OpenAlex.

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  12. Crystal structure of poxvirus thymidylate kinase: an unexpected dimerization has implications for antiviral therapy.Proceedings of the National Academy of Sciences of the United States of America · 2008
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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

11 authors at 2 institutions in 1 country.

Mark N PrichardDepartment of Pediatrics, University of Alabama School of Medicine, Birmingham, AL 35233, USA. mprichard@peds.uab.edu
Kathy A Keith
Mary P Johnson
Emma A Harden
Alexis McBrayer
Ming Luo
Shihong Qiu
Debasish Chattopadhyay
Xuesen Fan
Paul F Torrence
Earl R Kern
University of Alabama · USNorthern Arizona University · US

Funding

Yessinia autotransporters (Yaps): Structure, function, and host responseU54AI057157 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SEMPOWSKI, GREGORY D · 2003 to 2013
$91.4M
NIAID NIH HHS 1 U54 AI057157NIAID NIH HHS N01 AI030049NIAID NIH HHS U54 AI057157
6 · The paper itself

Abstract

The antiviral activity of a new series of thymidine analogs was determined against vaccinia virus (VV), cowpox virus (CV), herpes simplex virus, and varicella-zoster virus. Several compounds were identified that had good activity against each of the viruses, including a set of novel 5-substituted deoxyuridine analogs. To investigate the possibility that these drugs might be phosphorylated preferentially by the viral thymidine kinase (TK) homologs, the antiviral activities of these compounds were also assessed using TK-deficient strains of some of these viruses. Some of these compounds were shown to be much less effective in the absence of a functional TK gene in CV, which was unexpected given the high degree of amino acid identity between this enzyme and its cellular homolog. This unanticipated result suggested that the CV TK was important in the mechanism of action of these compounds and also that it might phosphorylate a wider variety of substrates than other type II enzymes. To confirm these data, we expressed the VV TK and human TK1 in bacteria and isolated the purified enzymes. Enzymatic assays demonstrated that the viral TK could efficiently phosphorylate many of these compounds, whereas most of the compounds were very poor substrates for the cellular kinase, TK1. Thus, the specific phosphorylation of these compounds by the viral kinase may be sufficient to explain the TK dependence. This unexpected result suggests that selective phosphorylation by the viral kinase may be a promising new approach in the discovery of highly selective inhibitors of orthopoxvirus replication.

Indexed as

Amino Acid SequenceAntiviral AgentsHerpesviridaeHumansKineticsMolecular Sequence DataOrthopoxvirusPhosphorylationThymidine KinaseVaccinia virusAntiviral AgentsThymidine Kinase

Identifiers

PMID17325220
PMCPMC1855528
OpenAlexW2167935679

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.