Evidence map›Paper›PMID 39358329›Full record

ArticleNature communications2024

De novo design of mini-protein binders broadly neutralizing Clostridioides difficile toxin B variants.

Xinchen Lv, Yuanyuan Zhang, Ke Sun, Qi Yang, Jianhua Luo, Liang Tao, Peilong Lu

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Materials today. Bio · 2026
    Article
  2. Orally available designed miniproteins inhibit enterotoxigenicbioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Review
  5. Clostridioides difficile pathogenesis and control.Nature reviews. Microbiology · 2026
    Review
  6. Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026
    Review
  7. Journal of the American Chemical Society · 2025
    Article
  8. Review
  9. De novo design of potent inhibitors of clostridial family toxins.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Review
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.

Xinchen Lv *Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, 310024, China.ORCID 0000-0001-5101-0004
Yuanyuan Zhang *Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China.ORCID 0000-0002-8062-2787
Ke SunKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China.
Qi YangKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China.
Jianhua LuoResearch Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, 310024, China.ORCID 0000-0003-3589-115X
Liang TaoResearch Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, 310024, China. taoliang@westlake.edu.cn.ORCID 0000-0003-3441-698X
Peilong LuResearch Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, 310024, China. lupeilong@westlake.edu.cn.ORCID 0000-0001-5894-9268

Funding

Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2020YFA0909200
6 · The paper itself

Abstract

Clostridioides difficile toxin B (TcdB) is the key virulence factor accounting for C. difficile infection-associated symptoms. Effectively neutralizing different TcdB variants with a universal solution poses a significant challenge. Here we present the de novo design and characterization of pan-specific mini-protein binders against major TcdB subtypes. Our design successfully binds to the first receptor binding interface (RBI-1) of the varied TcdB subtypes, exhibiting affinities ranging from 20 pM to 10 nM. The cryo-electron microscopy (cryo-EM) structures of the mini protein binder in complex with TcdB1 and TcdB4 are consistent with the computational design models. The engineered and evolved variants of the mini-protein binder and chondroitin sulfate proteoglycan 4 (CSPG4), another natural receptor that binds to the second RBI (RBI-2) of TcdB, better neutralize major TcdB variants both in cells and in vivo, as demonstrated by the colon-loop assay using female mice. Our findings provide valuable starting points for the development of therapeutics targeting C. difficile infections (CDI).

Indexed as

Bacterial ProteinsBacterial ToxinsClostridioides difficileCryoelectron MicroscopyAnimalsChondroitin Sulfate ProteoglycansClostridium InfectionsFemaleHumansMiceModels, MolecularProtein BindingBacterial ProteinsBacterial ToxinsChondroitin Sulfate ProteoglycanstoxB protein, Clostridium difficile

Identifiers

PMID39358329
PMCPMC11447207

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.