Evidence map›Paper›PMID 25355939›Full record

ArticleThe Journal of infectious diseases2015

High-throughput screening platform identifies small molecules that prevent sequestration of Plasmodium falciparum-infected erythrocytes.

Justin Gullingsrud, Neta Milman, Tracy Saveria, Olga Chesnokov, Kathryn Williamson, Anand Srivastava, Benoit Gamain, Patrick E Duffy, Andrew V Oleinikov

Open access · greenAbstract readValidation Study
In one paragraph

Article in The Journal of infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 23% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Biosensors for Detection of Human Placental Pathologies: A Review of Emerging Technologies and Current Trends.Translational research : the journal of laboratory and clinical medicine · 2019
    Review
  7. Article
  8. 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

9 authors at 5 institutions in 2 countries.

Justin GullingsrudSeattle Biomedical Research Institute, Seattle, Washington.
Neta MilmanSeattle Biomedical Research Institute, Seattle, Washington.
Tracy SaveriaSeattle Biomedical Research Institute, Seattle, Washington.
Olga ChesnokovCharles E. Schmidt College of Medicine, Department of Biomedical Science, Florida Atlantic University, Boca Raton.
Kathryn WilliamsonSeattle Biomedical Research Institute, Seattle, Washington.
Anand SrivastavaInserm UMR 1134 Université Paris Diderot, Sorbonne Paris Cité, UMR S1134 Institut National de la Transfusion Sanguine, Paris, France.
Benoit GamainInserm UMR 1134 Université Paris Diderot, Sorbonne Paris Cité, UMR S1134 Institut National de la Transfusion Sanguine, Paris, France.
Patrick E DuffyLaboratory of Malaria Immunology and Vaccinology, National Institutes of Health, Bethesda, Maryland.
Andrew V OleinikovSeattle Biomedical Research Institute, Seattle, Washington Charles E. Schmidt College of Medicine, Department of Biomedical Science, Florida Atlantic University, Boca Raton.
Center for Infectious Disease Research · USFlorida Atlantic University · USDélégation Paris 7 · FRInstitut National de la Transfusion Sanguine · FRNational Institutes of Health · US

Funding

Malaria Pathogenesis in young children and vaccine discoveryZIAAI001134 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DUFFY, PATRICK · 2010 to 2025
$11.3M
Pathways of Maternal AnemiaR01HD058005 · NICHD · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI OLEINIKOV, ANDREW V · 2009 to 2013
$2.8M
Pregnancy Malaria: Pathogenesis and ImmunityZIAAI001178 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DUFFY, PATRICK · 2012 to 2015
$2.1M
Identification of vaccine candidates against severe malariaR01AI092120 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI OLEINIKOV, ANDREW V · 2011 to 2014
$1.6M
High throughput screening for anti-adhesion drugs to treat severe malariaR56AI083668 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI OLEINIKOV, ANDREW V · 2010 to 2010
$433k
NIAID NIH HHS 1R56AI083668NIAID NIH HHS 5R01AI092120NIAID NIH HHS R01 AI092120NIAID NIH HHS R56 AI083668NICHD NIH HHS 5R01HD058005NICHD NIH HHS R01 HD058005
6 · The paper itself

Abstract

backgroundWe developed a 2-step approach to screen molecules that prevent and/or reverse Plasmodium falciparum-infected erythrocyte (IE) binding to host receptors. IE adhesion and sequestration in vasculature causes severe malaria, and therefore antiadhesion therapy might be useful as adjunctive treatment. IE adhesion is mediated by the polymorphic family (approximately 60 members) of P. falciparum EMP1 (PfEMP1) multidomain proteins.

methodsWe constructed sets of PfEMP1 domains that bind ICAM-1, CSA, or CD36, receptors that commonly support IE binding. Combinations of domain-coated beads were assayed by Bio-Plex technology as a high-throughput molecular platform to screen antiadhesion molecules (antibodies and small molecules). Molecules identified as so-called hits in the screen (first step) then could be assayed individually for inhibition of binding of live IE to receptors (second step).

resultsIn proof-of-principle studies, the antiadhesion activity of several antibodies was concordant in Bio-Plex and live IE assays. Using this 2-step approach, we identified several molecules in a small molecule library of 10 000 compounds that could inhibit and reverse binding of IEs to ICAM-1 and CSA receptors.

conclusionThis 2-step screening approach should be efficient for identification of antiadhesion drug candidates for falciparum malaria.

Indexed as

CD36 AntigensCell AdhesionCell Adhesion MoleculesCell LineErythrocytesHigh-Throughput Screening AssaysHumansIntercellular Adhesion Molecule-1Malaria, FalciparumPlasmodium falciparumProtozoan ProteinsSmall Molecule LibrariesCD36 AntigensCell Adhesion Moleculeserythrocyte membrane protein 1, Plasmodium falciparumIntercellular Adhesion Molecule-1Protozoan ProteinsSmall Molecule Librariesantiadhesion therapyCD36CSAhigh-throughput screeninghost receptorsICAM-1malariaPfEMP1 proteinsPlasmodium falciparumsequestration of parasitessmall molecules

Identifiers

PMID25355939
PMCPMC4366606
OpenAlexW2140888594

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.