Peptide Toxins—Discovery, Mechanisms of Action, and Therapeutic Potential

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 1838

Special Issue Editors


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Guest Editor
The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
Interests: spider peptide toxin; bioinsecticide; voltage-gated sodium channels; NaChBac; mammalian NaVs; peptide toxin; pharmacology
The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
Interests: spider peptide toxin; bioinsecticide; voltage-gated sodium channels; NaChBac; mammalian NaVs; peptide toxin; pharmacology

Special Issue Information

Dear Colleagues,

We are pleased to announce a Special Issue of Toxins titled "Peptide Toxins—Discovery, Mechanisms of Action, and Therapeutic Potential". This issue will explore the diverse and fascinating world of peptide toxins derived from various organisms, with a particular focus on those from animal venoms. These bioactive peptides have been extensively studied as antimicrobial agents, ion channel modulators, and enzyme inhibitors, serving as essential pharmacological tools for probing biological processes and developing novel therapeutic strategies.

Despite their immense potential, peptide toxin research faces multiple challenges, including difficulties in purification, identification, synthesis, functional validation, and SAR (structure–activity relationship) elucidation. Recent advancements in transcriptomics, peptidomics, structural biology, synthetic biology, and computational approaches, such as machine learning-assisted function prediction and high-throughput screening, are driving rapid progress in this field. Moreover, elucidating the evolutionary origins of peptide toxins and their ecological roles can provide crucial insights into their mechanisms of action and biomedical applications.

This Special Issue aims to comprehensively cover all aspects of peptide toxin research, including novel discovery, structural and functional characterization, molecular mechanisms, biotechnological applications, and therapeutic development. We welcome original research articles, reviews, and perspectives that contribute to advancing our understanding of peptide toxins and their potential applications in medicine and biotechnology.

We look forward to your contributions!

Prof. Dr. Mingqiang Rong
Dr. Cheng Tang
Guest Editors

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Keywords

  • peptide toxins
  • action mechanisms
  • pharmacological tool
  • drug candidates

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Published Papers (2 papers)

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Research

23 pages, 6607 KB  
Article
Crotoxin B from the South American Rattlesnake Crotalus vegrandis Blocks Voltage-Gated Calcium Channels Independent of Its Intrinsic Catalytic Activity
by Markus Eicheldinger, Erick Miranda-Laferte, Francisco Castilla, Nadine Jordan, Beatrix Santiago-Schübel and Patricia Hidalgo
Toxins 2026, 18(1), 36; https://doi.org/10.3390/toxins18010036 - 10 Jan 2026
Viewed by 289
Abstract
Neurotoxicity following South American Crotalus rattlesnake bite is primarily caused by crotoxin, the most abundant component in their venom. Despite the central role of voltage-gated calcium channels (CaV) in neurotransmission, direct targetability by crotoxin has been poorly explored. Crotoxin is a [...] Read more.
Neurotoxicity following South American Crotalus rattlesnake bite is primarily caused by crotoxin, the most abundant component in their venom. Despite the central role of voltage-gated calcium channels (CaV) in neurotransmission, direct targetability by crotoxin has been poorly explored. Crotoxin is a non-covalent heterodimer formed by an acidic subunit (CA) and a basic toxic phospholipase A2 subunit (CB). Here, we chromatographically isolated the CB subunit from Crotalus vegrandis and studied its effect on CaV heterologously expressed in tsA201 cells using the whole-cell patch-clamp technique. Mass spectrometry analysis identified a protein that matched with 97% sequence coverage the CBc isoform from Crotalus durissus terrificus. Isolated CB exhibited moderate phospholipase activity that was not correlated to its cytotoxic effect on cultured tsA201 cells. Using Ba2+ as a charge carrier to prevent the enzymatic activity, we found that CB inhibited currents mediated by the N-type CaV2.2 and CaV1.2 L-type calcium channels, in a dose–dependent manner, with higher potency for the latter, and negligible changes in the voltage dependence of channel activation. Our results reveal a novel phospholipase-independent biological activity and a molecular target of CB providing new insights into the pathophysiology of Crotalus snakebite envenoming with potential clinical therapeutic implications. Full article
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11 pages, 1642 KB  
Article
Sea Anemone-Derived Toxin Avd3i Inhibited Sodium Channel Nav1.4
by Jiaxin Gao, Guohao Liu, Yan Liu, Dezhao Zhang, Qinyi He, Qiong Liao and Canwei Du
Toxins 2025, 17(9), 461; https://doi.org/10.3390/toxins17090461 - 13 Sep 2025
Viewed by 1065
Abstract
Ion channels regulate ion transport across cell or organelle membranes, playing an important role in various biological processes. Sodium channel Nav1.4 is critical to initiating and propagating action potentials in skeletal muscles, and its dysfunction is associated with a variety of diseases, such [...] Read more.
Ion channels regulate ion transport across cell or organelle membranes, playing an important role in various biological processes. Sodium channel Nav1.4 is critical to initiating and propagating action potentials in skeletal muscles, and its dysfunction is associated with a variety of diseases, such as non-dystrophic myotonias. In this study, U-actitoxin-Avd3i (Avd3i), a Kunitz-type toxin derived from Anemonia viridis, was expressed in prokaryotic systems and was subsequently purified via high-pressure liquid chromatography. Patch clamp recording showed that Avd3i inhibited Nav1.4 in a concentration-dependent manner, with an IC50 of 25.43 μM. However, the toxin exerted no inhibitory activity in Nav1.5/Nav1.7 channels or Kv1.1/Kv1.3/Kv1.4/Kv4.2 potassium channels. Our study found that the sea anemone-derived toxin Avd3i inhibited sodium channel Nav1.4, providing a novel molecule that can act on the channel. Full article
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