Evidence map›Paper›PMID 39746545›Full record

ArticleMolecular & cellular proteomics : MCP2025

Molecular Display of the Animal Meta-Venome for Discovery of Novel Therapeutic Peptides.

Meng-Hsuan Hsiao, Yang Miao, Zixing Liu, Konstantin Schütze, Nathachit Limjunyawong, Daphne Chun-Che Chien, Wayne Denis Monteiro, Lee-Shin Chu, William Morgenlander, Sahana Jayaraman and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular & cellular proteomics : MCP, 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. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Meng-Hsuan HsiaoInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Yang MiaoInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Zixing LiuInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Biology, Zanvyl Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, Maryland, USA.
Konstantin SchützeSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Nathachit LimjunyawongThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Center of Research Excellence in Allergy and Immunology, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Daphne Chun-Che ChienThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Wayne Denis MonteiroInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Lee-Shin ChuDepartment of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
William MorgenlanderInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Sahana JayaramanInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Sung-Eun JangSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Jeffrey J GrayDepartment of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Heng ZhuDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Viral Oncology Program, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Xinzhong DongThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Martin SteineggerSchool of Biological Sciences, Seoul National University, Seoul, South Korea; Artificial Intelligence Institute, Seoul National University, Seoul, South Korea; Institute of Molecular Biology and Genetics, Seoul National University, Seoul, South Korea. Electronic address: martin.steinegger@snu.ac.kr.
H Benjamin LarmanInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Electronic address: hlarman1@jhmi.edu.

Funding

Prediction of the Structures of Protein ComplexesR35GM141881 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI JEFFREY J GRAY · 2021 to 2026
$7.6M
Design and Analysis of Displayed PeptidomesR01GM136724 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI LARMAN, HARRY BENJAMIN, RUCZINSKI, INGO · 2020 to 2023
$1.9M
NIGMS NIH HHS R01 GM136724NIGMS NIH HHS R35 GM141881
6 · The paper itself

Abstract

Animal venoms, distinguished by their unique structural features and potent bioactivities, represent a vast and relatively untapped reservoir of therapeutic molecules. However, limitations associated with comprehensively constructing and expressing highly complex venom and venom-like molecule libraries have precluded their therapeutic evaluation via high-throughput screening. Here, we developed an innovative computational approach to design a highly diverse library of animal venoms and "metavenoms". We used programmable M13 hyperphage display to preserve critical disulfide-bonded structures for highly parallelized single-round biopanning with quantitation via high-throughput DNA sequencing. Our approach led to the discovery of Kunitz-type domain containing proteins that target the human itch receptor Mas-related G-protein coupled receptor member X4, which plays a crucial role in itch perception. Deep learning-based structural homology mining identified two endogenous human homologs, tissue factor pathway inhibitor (TFPI), and serine peptidase inhibitor, Kunitz type 2 (SPINT2), which exhibit agonist-dependent potentiation of Mas-related G-protein coupled receptor member X4. Highly multiplexed screening of animal venoms and metavenoms is therefore a promising approach to uncover new drug candidates.

Indexed as

Drug DiscoveryPeptidesVenomsAnimalsHumansPeptide LibraryReceptors, G-Protein-CoupledPeptide LibraryPeptidesReceptors, G-Protein-CoupledVenomsdatabase miningitch receptorligand discoveryphage displayvenom

Identifiers

PMID39746545
PMCPMC11833617

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.