Evidence map›Paper›PMID 31356619›Full record

ArticlePLoS pathogens2019

Novel lactate dehydrogenase inhibitors with in vivo efficacy against Cryptosporidium parvum.

Kun Li, Sara M Nader, Xuejin Zhang, Benjamin C Ray, Chi Yong Kim, Aditi Das, William H Witola

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 8% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Prevalence ofFrontiers in cellular and infection microbiology · 2021
    Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Intestine microbiota and SCFAs response in naturallyFrontiers in cellular and infection microbiology · 2023
    Article
  9. Article
  10. Anti-protozoal activity of Thymol and a Thymol ester against Cryptosporidium parvum in cell culture.International journal for parasitology. Drugs and drug resistance · 2021
    Article
  11. Article
  12. Frontiers in microbiology · 2021
    Article
  13. Article
  14. Article
  15. Article
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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

7 authors at 1 institution in 1 country.

Kun LiDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
Sara M NaderDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.ORCID 0000-0002-8406-441X
Xuejin ZhangDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
Benjamin C RayDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.ORCID 0000-0001-6678-6972
Chi Yong KimDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.ORCID 0000-0003-4431-7504
Aditi DasDepartment of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
William H WitolaDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.ORCID 0000-0002-2308-0539
University of Illinois Urbana-Champaign · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cryptosporidium parvum is a highly prevalent zoonotic and anthroponotic protozoan parasite that causes a diarrheal syndrome in children and neonatal livestock, culminating in growth retardation and mortalities. Despite the high prevalence of C. parvum, there are no fully effective and safe drugs for treating infections, and there is no vaccine. We have previously reported that the bacterial-like C. parvum lactate dehydrogenase (CpLDH) enzyme is essential for survival, virulence and growth of C. parvum in vitro and in vivo. In the present study, we screened compound libraries and identified inhibitors against the enzymatic activity of recombinant CpLDH protein in vitro. We tested the inhibitors for anti-Cryptosporidium effect using in vitro infection assays of HCT-8 cells monolayers and identified compounds NSC158011 and NSC10447 that inhibited the proliferation of intracellular C. parvum in vitro, with IC50 values of 14.88 and 72.65 μM, respectively. At doses tolerable in mice, we found that both NSC158011 and NSC10447 consistently significantly reduced the shedding of C. parvum oocysts in infected immunocompromised mice's feces, and prevented intestinal villous atrophy as well as mucosal erosion due to C. parvum. Together, our findings have unveiled promising anti-Cryptosporidium drug candidates that can be explored further for the development of the much needed novel therapeutic agents against C. parvum infections.

Indexed as

AnimalsAntiprotozoal AgentsCell LineCryptosporidiosisCryptosporidium parvumEnzyme InhibitorsHost-Parasite InteractionsHumansL-Lactate DehydrogenaseMiceMice, KnockoutMolecular Docking SimulationParasitic Sensitivity TestsProtozoan ProteinsRecombinant ProteinsAntiprotozoal AgentsEnzyme InhibitorsL-Lactate DehydrogenaseProtozoan ProteinsRecombinant Proteins

Identifiers

PMID31356619
PMCPMC6687188
OpenAlexW2966590308

What OpenQuestion holds

Textmetadata
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.