Evidence map›Paper›PMID 40411405›Full record

ArticleProtein science : a publication of the Protein Society2025

Enhancing schistosomiasis drug discovery approaches with optimized proteasome substrates.

Elany B Silva, Zhenze Jiang, Chenxi Liu, Pavla Fajtová, Thaiz R Teixeira, Giovana de Castro Fiorini Maia, Lawrence J Liu, Nelly El-Sakkary, Danielle E Skinner, Ali Syed and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Protein science : a publication of the Protein Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. A recombinant expression system for thebioRxiv : the preprint server for biology · 2025
    Article
  2. Enhancing schistosomiasis drug discovery approaches with optimized proteasome substrates.Protein science : a publication of the Protein Society · 2025
    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

13 authors.

Elany B SilvaCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Zhenze JiangCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Chenxi LiuCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Pavla FajtováCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Thaiz R TeixeiraCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Giovana de Castro Fiorini MaiaDepartment of Biochemistry & Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Lawrence J LiuCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Nelly El-SakkaryCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Danielle E SkinnerCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Ali SyedCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Steven C WangCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Conor R CaffreyCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Anthony J O'DonoghueCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.ORCID 0000-0001-5695-0409

Funding

Proteasome inhibitors against mucosal protozoan pathogensR01AI158612 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ECKMANN, LARS, O'DONOGHUE, ANTHONY JOHN · 2021 to 2025
$3.2M
The catalytic core of the proteasome as a drug target to treat Human African TrypanosomiasisR21AI171824 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CAFFREY, CONOR, O'DONOGHUE, ANTHONY JOHN · 2022 to 2023
$435k
Selective proteasome inhibitors for trichomoniasisR21AI146387 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ECKMANN, LARS, O'DONOGHUE, ANTHONY JOHN · 2019 to 2020
$433k
Exploring the proteasome as a new drug target to treat schistosomiasisR21AI133393 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI O'DONOGHUE, ANTHONY JOHN · 2017 to 2018
$426k
Akademie Věd České Republiky MSM200551901H2020 Marie Skłodowska-Curie Actions 846688National Institute of Allergy and Infectious Diseases R01AI158612National Institute of Allergy and Infectious Diseases R21AI133393National Institute of Allergy and Infectious Diseases R21AI146387National Institute of Allergy and Infectious Diseases R21AI171824NIAID NIH HHS R01 AI158612NIAID NIH HHS R21 AI133393NIAID NIH HHS R21 AI146387NIAID NIH HHS R21 AI171824
6 · The paper itself

Abstract

Schistosomiasis, a neglected tropical disease infecting over 200 million people globally, has limited therapeutic options. The 20S proteasome is a validated drug target for many parasitic infections, including those caused by Plasmodium and Leishmania, and we have previously demonstrated antischistosomal activity with inhibitors targeting Schistosoma mansoni 20S proteasome (Sm20S). Here, we developed optimized subunit-specific substrates for Sm20S based on data generated by Multiplex Substrate Profiling by Mass Spectrometry (MSP-MS). These substrates exhibit 9-fold or more improved activity compared to traditional human constitutive 20S proteasome (c20S) substrates. The optimized substrates also eliminated the need for extensive Sm20S purification, as robust enzyme activity could be detected in parasite extracts following an ammonium sulfate precipitation step. Finally, we show that the substrate and inhibition profiles for the 20S proteasome from the three medically important schistosome species are similar. This suggests that Sm20S-focused inhibitor development can be efficiently extrapolated to the other schistosome species, leading to significant time and resource savings.

Indexed as

Drug DiscoveryHelminth ProteinsProteasome Endopeptidase ComplexProteasome InhibitorsSchistosoma mansoniSchistosomiasisAnimalsHumansSubstrate SpecificityHelminth ProteinsProteasome Endopeptidase ComplexProteasome Inhibitorsdrug discoverydrug targetMSP‐MSneglected diseaseparasiteprotease inhibitorproteasomeSchistosomaschistosomiasissubstrate profilesubstrate specificity

Identifiers

PMID40411405
PMCPMC12102734

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.