Evidence map›Paper›PMID 30332435›Full record

ArticlePloS one2018

In vitro toxicity and efficacy of verdinexor, an exportin 1 inhibitor, on opportunistic viruses affecting immunocompromised individuals.

Douglas G Widman, Savanna Gornisiewicz, Sharon Shacham, Sharon Tamir

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.3field-weighted citation impact, top 10% 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

30 citing papers in PubMed, 43 citations in OpenAlex.

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  16. Selinexor and COVID-19: The Neglected Warden.Frontiers in pharmacology · 2022
    Review
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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

4 authors at 1 institution in 1 country.

Douglas G WidmanKaryopharm Therapeutics, Department of Neurofegenerative and Infectious Diseases, Newton, Massachussets, United States of America.ORCID 0000-0002-3585-6373
Savanna GornisiewiczKaryopharm Therapeutics, Department of Neurofegenerative and Infectious Diseases, Newton, Massachussets, United States of America.
Sharon ShachamKaryopharm Therapeutics, Department of Neurofegenerative and Infectious Diseases, Newton, Massachussets, United States of America.
Sharon TamirKaryopharm Therapeutics, Department of Neurofegenerative and Infectious Diseases, Newton, Massachussets, United States of America.
Karyopharm Therapeutics (United States) · US

Funding

NIAID NIH HHS HHSN272201100013CNIAID NIH HHS HHSN272201100013INIAID NIH HHS HHSN272201100016CNIMH NIH HHS HHSN271201100006I
6 · The paper itself

Abstract

Infection of immunocompromised individuals with normally benign opportunistic viruses is a major health burden globally. Infections with viruses such as Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), Kaposi's sarcoma virus (KSHV), adenoviruses (AdV), BK virus (BKPyV), John Cunningham virus (JCPyV), and human papillomavirus (HPV) are significant concerns for the immunocompromised, including when these viruses exist as a co-infection with human immunodeficiency virus (HIV). These viral infections are more complicated in patients with a weakened immune system, and often manifest as malignancies resulting in significant morbidity and mortality. Vaccination is not an attractive option for these immune compromised individuals due to defects in their adaptive immune response. Verdinexor is part of a novel class of small molecules known as SINE (Selective Inhibitor of Nuclear Export) compounds. These small molecules demonstrate specificity for the nuclear export protein XPO1, to which they bind and block function, resulting in sequestration of XPO1-dependent proteins in the nucleus of the cell. In antiviral screening, verdinexor demonstrated varying levels of efficacy against all of the aforementioned viruses including previously with HIV. Studies by other labs have discussed likely mechanisms of action for verdinexor (ie. XPO1-dependence) against each virus. GLP toxicology studies suggest that anti-viral activity can be achieved at a tolerable dose range, based on the safety profile of a previous phase 1 clinical trial of verdinexor in healthy human volunteers. Taken together, these results indicate verdinexor has the potential to be a broad spectrum antiviral for immunocompromised subjects for which vaccination is a poor option.

Indexed as

AcrylamidesAdenoviridae InfectionsAnimalsCell Line, TumorCytomegalovirus InfectionsDrug Evaluation, PreclinicalEpstein-Barr Virus InfectionsExportin 1 ProteinFibroblastsGuinea PigsHEK293 CellsHeLa CellsHIV InfectionsHumansHydrazinesImmunocompromised HostAcrylamidesExportin 1 ProteinHydrazinesKaryopherinsReceptors, Cytoplasmic and NuclearTriazolesverdinexor

Identifiers

PMID30332435
PMCPMC6192554
OpenAlexW2949135247

What OpenQuestion holds

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LicenceCC BY
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.