Evidence map›Paper›PMID 25801568›Full record

ArticleAntimicrobial agents and chemotherapy2015

Brincidofovir (CMX001) inhibits BK polyomavirus replication in primary human urothelial cells.

Garth D Tylden, Hans H Hirsch, Christine Hanssen Rinaldo

Open access · hybridAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 12% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

  1. Native kidney BK virus nephropathy, a systematic review.Transplant infectious disease : an official journal of the Transplantation Society · 2019
    Pooled it
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  13. Antiviral Treatments.Clinics in chest medicine · 2017
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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

3 authors at 2 institutions in 2 countries.

Garth D TyldenDepartment of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
Hans H HirschTransplantation & Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel, Basel, Switzerland Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
Christine Hanssen RinaldoDepartment of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway christine.rinaldo@unn.no.ORCID http://orcid.org/0000-0002-6970-6728
University Hospital of North Norway · NOUniversity of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BK polyomavirus (BKPyV)-associated hemorrhagic cystitis (PyVHC) complicates 5 to 15% of allogeneic hematopoietic stem cell transplantations. Targeted antivirals are still unavailable. Brincidofovir (BCV; previously CMX001) has shown inhibitory activity against diverse viruses, including BKPyV in a primary human renal tubule cell culture model of polyomavirus-associated nephropathy. We investigated the effects of BCV in BKPyV-infected and uninfected primary human urothelial cells (HUCs), the target cells of BKPyV in PyVHC. The BCV concentrations causing 50 and 90% reductions (EC50 and EC90) in the number of intracellular BKPyV genome equivalents per cell (icBKPyV) were 0.27 μM and 0.59 μM, respectively. At 0.63 μM, BCV reduced viral late gene expression by 90% and halted progeny release. Preinfection treatment for only 24 h reduced icBKPyV similarly to treatment from 2 to 72 h postinfection, while combined pre- and postinfection treatment suppressed icBKPyV completely. After investigating BCV's effects on HUC viability, mean selectivity indices at 50 and 90% inhibition (SI50 and SI90) calculated for cellular DNA replication were 2.7 and 2.9, respectively, those for mitochondrial activity were 8.9 and 10.4, those for total ATP were 8.6 and 8.2, and those for membrane integrity were 25.9 and 16.7. The antiviral and cytostatic effects, but less so the cytotoxic effects, were inversely related to cell density. The cytotoxic effects at concentrations of ≥10 μM were rapid and likely related to BCV's lipid moiety. After carefully defining the antiviral, cytostatic, and cytotoxic properties of BCV in HUCs, we conclude that a preemptive or prophylactic approach in PyVHC is likely to give the best results.

Indexed as

Antiviral AgentsBK VirusBlotting, WesternCells, CulturedCell SurvivalCytosineHumansOrganophosphonatesVirus ReplicationAntiviral AgentsbrincidofovirCytosineOrganophosphonates

Identifiers

PMID25801568
PMCPMC4432119
OpenAlexW2061316076

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.