Evidence map›Paper›PMID 32101733›Full record

ArticleCell reports2020

Structural Insights into Rational Design of Single-Domain Antibody-Based Antitoxins against Botulinum Neurotoxins.

Kwok-Ho Lam, Jacqueline M Tremblay, Edwin Vazquez-Cintron, Kay Perry, Celinia Ondeck, Robert P Webb, Patrick M McNutt, Charles B Shoemaker, Rongsheng Jin

Abstract read
In one paragraph

Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing 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

28 citing papers in PubMed.

  1. Article
  2. Botulinum neurotoxin: from molecular pathogenesis to emerging countermeasures.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026
    Review
  3. Comprehensive Mapping of Immune Nanobody Repertoires with NanoMAP.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. The Degradation of Botulinum Neurotoxin Light Chains Using PROTACs.International journal of molecular sciences · 2024
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Structure-guided design of a potentFrontiers in microbiology · 2023
    Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. 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.

Kwok-Ho LamDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA.
Jacqueline M TremblayTufts Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Edwin Vazquez-CintronDepartment of Neuroscience, U.S. Army Medical Research Institute of Chemical Defense, Gunpowder, MD 21010, USA.
Kay PerryNE-CAT, Department of Chemistry and Chemical Biology, Cornell University, Argonne National Laboratory, Argonne, IL 60439, USA.
Celinia OndeckDepartment of Neuroscience, U.S. Army Medical Research Institute of Chemical Defense, Gunpowder, MD 21010, USA.
Robert P WebbThe Division of Molecular and Translational Sciences, United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA.
Patrick M McNuttDepartment of Neuroscience, U.S. Army Medical Research Institute of Chemical Defense, Gunpowder, MD 21010, USA.
Charles B ShoemakerTufts Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Rongsheng JinDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: r.jin@uci.edu.

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI Nozomi Ando, J Christopher Fromme · 2018 to 2026
$34.2M
X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
Structure and Function of C. Difficile ToxinsR01AI139087 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI Min Dong, Rongsheng Jin · 2018 to 2026
$7.4M
Molecular mechanisms of botulinum neurotoxin neutralizationR01AI125704 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI JIN, RONGSHENG, SHOEMAKER, CHARLES BIX · 2016 to 2020
$3.0M
Computational design of inhibitors against botulinum neurotoxinR21AI139690 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI JIN, RONGSHENG · 2018 to 2019
$440k
Structural mechanism for recognition of host receptor by botulinum neurotoxin AR21AI123920 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI JIN, RONGSHENG · 2016 to 2017
$425k
NIAID NIH HHS R01 AI125704NIAID NIH HHS R01 AI139087NIAID NIH HHS R21 AI123920NIAID NIH HHS R21 AI139690NIGMS NIH HHS P30 GM124165NIGMS NIH HHS P41 GM103393NIGMS NIH HHS P41 GM103403
6 · The paper itself

Abstract

Botulinum neurotoxin (BoNT) is one of the most acutely lethal toxins known to humans, and effective treatment for BoNT intoxication is urgently needed. Single-domain antibodies (VHH) have been examined as a countermeasure for BoNT because of their high stability and ease of production. Here, we investigate the structures and the neutralization mechanisms for six unique VHHs targeting BoNT/A1 or BoNT/B1. These studies reveal diverse neutralizing mechanisms by which VHHs prevent host receptor binding or block transmembrane delivery of the BoNT protease domain. Guided by this knowledge, we design heterodimeric VHHs by connecting two neutralizing VHHs via a flexible spacer so they can bind simultaneously to the toxin. These bifunctional VHHs display much greater potency in a mouse co-intoxication model than similar heterodimers unable to bind simultaneously. Taken together, our studies offer insight into antibody neutralization of BoNTs and advance our ability to design multivalent anti-pathogen VHHs with improved therapeutic properties.

Indexed as

Drug DesignAnimalsAntibodies, NeutralizingAntitoxinsBotulinum ToxinsCell MembraneFemaleHydrogen-Ion ConcentrationMiceModels, MolecularProtein DomainsProtein FoldingProtein MultimerizationReceptors, Cell SurfaceSingle-Domain AntibodiesAntibodies, NeutralizingAntitoxinsBotulinum ToxinsReceptors, Cell SurfaceSingle-Domain Antibodiesantitoxinbifunctional antibodybotulinum neurotoxinneutralizing epitopesingle-domain antibodystructure-based designVHH

Identifiers

PMID32101733
PMCPMC7138525

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.