Evidence map›Paper›PMID 31015448›Full record

ArticleNature communications2019

A suite of phenotypic assays to ensure pipeline diversity when prioritizing drug-like Cryptosporidium growth inhibitors.

Rajiv S Jumani, Muhammad M Hasan, Erin E Stebbins, Liam Donnelly, Peter Miller, Connor Klopfer, Kovi Bessoff, Jose E Teixeira, Melissa S Love, Case W McNamara and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
–field-weighted citation impact
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

33 citing papers in PubMed.

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  7. Molecular biology of the cell · 2025
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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.

Rajiv S JumaniDepartment of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, 05405, USA.
Muhammad M HasanDepartment of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, 05405, USA.
Erin E StebbinsDepartment of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, 05405, USA.
Liam DonnellyDepartment of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, 05405, USA.
Peter MillerDepartment of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, 05405, USA.
Connor KlopferDepartment of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, 05405, USA.
Kovi BessoffDepartment of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, 05405, USA.
Jose E TeixeiraDepartment of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, 05405, USA.
Melissa S LoveCalibr at The Scripps Research Institute, La Jolla, CA, 92037, USA.
Case W McNamaraCalibr at The Scripps Research Institute, La Jolla, CA, 92037, USA.
Christopher D HustonDepartment of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, 05405, USA. christopher.huston@uvm.edu.ORCID http://orcid.org/0000-0002-5393-139X

Funding

Using Dengue Controlled Human Infection Model to Identify Adaptive Immune Correlates of ProtectionP20GM125498 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI Kristen Pierce · 2018 to 2026
$24.9M
VERMONT IMMUNOBIOLOIGY/ INFECTIOUS DISEASES CENTERP20RR021905 · NCRR · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI HILL, JACK · 2006 to 2011
$14.5M
Vermont Immunology/Infectious Diseases CenterP30GM118228 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI BUDD, RALPH C · 2016 to 2021
$6.8M
Vermont Immunology/Infectious Diseases Training GrantT32AI055402 · NIAID · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI GARY E WARD · 2005 to 2026
$2.7M
Continuous in vitro culture and treatment of Cryptosporidium using small molecule differentiation inhibitorsR21AI130807 · NIAID · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI HUSTON, CHRISTOPHER D · 2017 to 2018
$424k
NCRR NIH HHS P20 RR021905NIAID NIH HHS R21 AI130807NIAID NIH HHS T32 AI055402NIGMS NIH HHS P20 GM125498NIGMS NIH HHS P30 GM118228
6 · The paper itself

Abstract

Cryptosporidiosis is a leading cause of life-threatening diarrhea in children, and the only currently approved drug is ineffective in malnourished children and immunocompromised people. Large-scale phenotypic screens are ongoing to identify anticryptosporidial compounds, but optimal approaches to prioritize inhibitors and establish a mechanistically diverse drug development pipeline are unknown. Here, we present a panel of medium-throughput mode of action assays that enable testing of compounds in several stages of the Cryptosporidium life cycle. Phenotypic profiles are given for thirty-nine anticryptosporidials. Using a clustering algorithm, the compounds sort by phenotypic profile into distinct groups of inhibitors that are either chemical analogs (i.e. same molecular mechanism of action (MMOA)) or known to have similar MMOA. Furthermore, compounds belonging to multiple phenotypic clusters are efficacious in a chronic mouse model of cryptosporidiosis. This suite of phenotypic assays should ensure a drug development pipeline with diverse MMOA without the need to identify underlying mechanisms.

Indexed as

AlgorithmsAnimalsAntiparasitic AgentsCell Culture TechniquesCell Line, TumorCluster AnalysisCryptosporidiosisCryptosporidiumDiarrheaDisease Models, AnimalDrug DiscoveryGrowth InhibitorsHumansLife Cycle StagesMaleMiceAntiparasitic AgentsGrowth Inhibitors

Identifiers

PMID31015448
PMCPMC6478823

What OpenQuestion holds

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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.