Evidence map›Paper›PMID 20713664›Full record

ArticleAntimicrobial agents and chemotherapy2010

1-O-hexadecyloxypropyl cidofovir (CMX001) effectively inhibits polyomavirus BK replication in primary human renal tubular epithelial cells.

Christine Hanssen Rinaldo, Rainer Gosert, Eva Bernhoff, Solrun Finstad, Hans H Hirsch

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 9% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.

  1. A systematic review of oral herpetic viral infections in cancer patients: commonly used outcome measures and interventions.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2017
    Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Symptomatic BK Virus Infection Is Associated With Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2016
    Article
  13. Characterization of Immunodominant BK Polyomavirus 9mer Epitope T Cell Responses.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2016
    Article
  14. BK Polyomavirus Replication in Renal Tubular Epithelial Cells Is Inhibited by Sirolimus, but Activated by Tacrolimus Through a Pathway Involving FKBP-12.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2016
    Article
  15. Article
  16. Article
  17. Brincidofovir for polyomavirus-associated nephropathy after allogeneic hematopoietic stem cell transplantation.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2015
    Article
  18. Article
  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 3 institutions in 2 countries.

Christine Hanssen RinaldoTransplantation Virology, Institute for Medical Microbiology, Department of Biomedicine, University of Basel, Petersplatz 10, Basel, Switzerland.
Rainer Gosert
Eva Bernhoff
Solrun Finstad
Hans H Hirsch
University Hospital of North Norway · NOUniversity Hospital of Basel · CHUniversity of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antiviral drugs for treating polyomavirus BK (BKV) replication in polyomavirus-associated nephropathy or hemorrhagic cystitis are of considerable clinical interest. Unlike cidofovir, the lipid conjugate 1-O-hexadecyloxypropyl cidofovir (CMX001) is orally available and has not caused detectable nephrotoxicity in rodent models or human studies to date. Primary human renal proximal tubular epithelial cells were infected with BKV-Dunlop, and CMX001 was added 2 h postinfection (hpi). The intracellular and extracellular BKV DNA load was determined by quantitative PCR. Viral gene expression was examined by quantitative reverse transcription-PCR, Western blotting, and immunofluorescence microscopy. We also examined host cell viability, proliferation, metabolic activity, and DNA replication. The titration of CMX001 identified 0.31 μM as the 90% effective concentration (EC(90)) for reducing the extracellular BKV load at 72 hpi. BKV large T antigen mRNA and protein expression was unaffected at 24 hpi, but the intracellular BKV genome was reduced by 90% at 48 hpi. Late gene expression was reduced by 70 and 90% at 48 and 72 hpi, respectively. Comparisons of CMX001 and cidofovir EC(90)s from 24 to 96 hpi demonstrated that CMX001 had a more rapid and enduring effect on BKV DNA and infectious progeny at 96 hpi than cidofovir. CMX001 at 0.31 μM had little effect on overall cell metabolism but reduced bromodeoxyuridine incorporation and host cell proliferation by 20 to 30%, while BKV infection increased cell proliferation in both rapidly dividing and near-confluent cultures. We conclude that CMX001 inhibits BKV replication with a longer-lasting effect than cidofovir at 400× lower levels, with fewer side effects on relevant host cells in vitro.

Indexed as

Antiviral AgentsBK VirusBlotting, WesternCell ProliferationCells, CulturedCell SurvivalCytosineHumansMicroscopy, FluorescenceOrganophosphonatesReverse Transcriptase Polymerase Chain ReactionVirus ReplicationAntiviral AgentsbrincidofovirCytosineOrganophosphonates

Identifiers

PMID20713664
PMCPMC2976161
OpenAlexW2160781077

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.