E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Toxins in Drug Discovery and Pharmacology"

A special issue of Toxins (ISSN 2072-6651).

Deadline for manuscript submissions: closed (30 September 2017)

Special Issue Editor

Guest Editor
Dr. Steve Peigneur

Catholic University Leuven (KU Leuven), Toxicology and Pharmacology, Herestraat 49-Box 922, 3000 Leuven, Belgium
Website | E-Mail

Special Issue Information

Dear Colleagues,

Venoms from marine and terrestrial animals (cone snails, scorpions, spiders, snakes, centipedes, cnidarian, etc.) can be seen as an untapped cocktail of biologically-active compounds, being increasingly recognized as new emerging source of peptide-based therapeutics. Venomous animals are considered to be specialized predators that have evolved the most sophisticated peptide chemistry and neuropharmacology for their own biological purposes by producing venoms that contains a structural and functional diversity of neurotoxins. These neurotoxins have shown to be highly selective ligands for a wide range of ion channels and receptors. Therefore, they represent interesting lead compounds for the development of, for example, analgesics, anti-cancer drugs, drugs for neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, etc.

This Special Issue of Toxins aims to provide a comprehensive look at toxins and toxin inspired leads and will focus on the mechanism of action, structure-function and evolution of pharmacological interesting venom components, including but not limited to, recent developments relating to the emergence of venoms as an underutilized source of highly evolved bioactive peptides with clinical potential.

Dr. Steve Peigneur
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1500 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sodium channels

  • potassium channels

  • calcium channels

  • chloride ion channels

  • TRP channels

  • ASIC channels

  • opiate receptors

  • acetylcholine receptors

  • NMDA receptor

  • Antibiotics

  • antimicrobial peptides

  • botulinum toxins

  • cone snail venom peptides

  • spider venom peptides

  • amphibian peptides

  • sea anemone toxins

  • scorpion toxins

  • snake toxins

  • centipede toxins

Published Papers (8 papers)

View options order results:
result details:
Displaying articles 1-8
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Anti-Salmonella Activity Modulation of Mastoparan V1—A Wasp Venom Toxin—Using Protease Inhibitors, and Its Efficient Production via an Escherichia coli Secretion System
Toxins 2017, 9(10), 321; doi:10.3390/toxins9100321
Received: 15 September 2017 / Revised: 10 October 2017 / Accepted: 11 October 2017 / Published: 13 October 2017
PDF Full-text (2454 KB) | HTML Full-text | XML Full-text
Abstract
A previous study highlighted that mastoparan V1 (MP-V1), a mastoparan from the venom of the social wasp Vespula vulgaris, is a potent antimicrobial peptide against Salmonella infection, which causes enteric diseases. However, there exist some limits for its practical application due to
[...] Read more.
A previous study highlighted that mastoparan V1 (MP-V1), a mastoparan from the venom of the social wasp Vespula vulgaris, is a potent antimicrobial peptide against Salmonella infection, which causes enteric diseases. However, there exist some limits for its practical application due to the loss of its activity in an increased bacterial density and the difficulty of its efficient production. In this study, we first modulated successfully the antimicrobial activity of synthetic MP-V1 against an increased Salmonella population using protease inhibitors, and developed an Escherichia coli secretion system efficiently producing active MP-V1. The protease inhibitors used, except pepstatin A, significantly increased the antimicrobial activity of the synthetic MP-V1 at minimum inhibitory concentrations (determined against 106 cfu/mL of population) against an increased population (108 cfu/mL) of three different Salmonella serotypes, Gallinarum, Typhimurium and Enteritidis. Meanwhile, the E. coli strain harboring OmpA SS::MP-V1 was identified to successfully secrete active MP-V1 into cell-free supernatant, whose antimicrobial activity disappeared in the increased population (108 cfu/mL) of Salmonella Typhimurium recovered by adding a protease inhibitor cocktail. Therefore, it has been concluded that our challenge using the E. coli secretion system with the protease inhibitors is an attractive strategy for practical application of peptide toxins, such as MP-V1. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
Figures

Figure 1

Open AccessArticle The Influence of Resiniferatoxin (RTX) and Tetrodotoxin (TTX) on the Distribution, Relative Frequency, and Chemical Coding of Noradrenergic and Cholinergic Nerve Fibers Supplying the Porcine Urinary Bladder Wall
Toxins 2017, 9(10), 310; doi:10.3390/toxins9100310
Received: 29 August 2017 / Revised: 20 September 2017 / Accepted: 1 October 2017 / Published: 3 October 2017
PDF Full-text (2500 KB) | HTML Full-text | XML Full-text
Abstract
The present study investigated the influence of intravesically instilled resiniferatoxin (RTX) or tetrodotoxin (TTX) on the distribution, number, and chemical coding of noradrenergic and cholinergic nerve fibers (NF) supplying the urinary bladder in female pigs. Samples from the bladder wall were processed for
[...] Read more.
The present study investigated the influence of intravesically instilled resiniferatoxin (RTX) or tetrodotoxin (TTX) on the distribution, number, and chemical coding of noradrenergic and cholinergic nerve fibers (NF) supplying the urinary bladder in female pigs. Samples from the bladder wall were processed for double-labelling immunofluorescence with antibodies against cholinergic and noradrenergic markers and some other neurotransmitter substances. Both RTX and TTX caused a significant decrease in the number of cholinergic NF in the urinary bladder wall (in the muscle coat, submucosa, and beneath the urothelium). RTX instillation resulted in a decrease in the number of noradrenergic NF in the submucosa and urothelium, while TTX treatment caused a significant increase in the number of these axons in all the layers. The most remarkable changes in the chemical coding of the NF comprised a distinct decrease in the number of the cholinergic NF immunoreactive to CGRP (calcitonin gene-related peptide), nNOS (neuronal nitric oxide synthase), SOM (somatostatin) or VIP (vasoactive intestinal polypeptide), and an increase in the number of noradrenergic NF immunopositive to GAL (galanin) or nNOS, both after RTX or TTX instillation. The present study is the first to suggest that both RTX and TTX can modify the number of noradrenergic and cholinergic NF supplying the porcine urinary bladder. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
Figures

Figure 1

Open AccessArticle Antiallodynic Effects of Bee Venom in an Animal Model of Complex Regional Pain Syndrome Type 1 (CRPS-I)
Toxins 2017, 9(9), 285; doi:10.3390/toxins9090285
Received: 25 August 2017 / Revised: 11 September 2017 / Accepted: 13 September 2017 / Published: 15 September 2017
PDF Full-text (3528 KB) | HTML Full-text | XML Full-text
Abstract
Neuropathic pain in a chronic post-ischaemic pain (CPIP) model mimics the symptoms of complex regional pain syndrome type I (CRPS I). The administration of bee venom (BV) has been utilized in Eastern medicine to treat chronic inflammatory diseases accompanying pain. However, the analgesic
[...] Read more.
Neuropathic pain in a chronic post-ischaemic pain (CPIP) model mimics the symptoms of complex regional pain syndrome type I (CRPS I). The administration of bee venom (BV) has been utilized in Eastern medicine to treat chronic inflammatory diseases accompanying pain. However, the analgesic effect of BV in a CPIP model remains unknown. The application of a tight-fitting O-ring around the left ankle for a period of 3 h generated CPIP in C57/Bl6 male adult mice. BV (1 mg/kg ; 1, 2, and 3 times) was administered into the SC layer of the hind paw, and the antiallodynic effects were investigated using the von Frey test and by measuring the expression of neurokinin type 1 (NK-1) receptors in dorsal root ganglia (DRG). The administration of BV dose-dependently reduced the pain withdrawal threshold to mechanical stimuli compared with the pre-administration value and with that of the control group. After the development of the CPIP model, the expression of NK-1 receptors in DRG increased and then decreased following the administration of BV. SC administration of BV results in the attenuation of allodynia in a mouse model of CPIP. The antiallodynic effect was objectively proven through a reduction in the increased expression of NK-1 receptors in DRG. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
Figures

Figure 1

Open AccessArticle Cobra Venom Factor and Ketoprofen Abolish the Antitumor Effect of Nerve Growth Factor from Cobra Venom
Toxins 2017, 9(9), 274; doi:10.3390/toxins9090274
Received: 17 August 2017 / Revised: 1 September 2017 / Accepted: 2 September 2017 / Published: 6 September 2017
PDF Full-text (3125 KB) | HTML Full-text | XML Full-text
Abstract
We showed recently that nerve growth factor (NGF) from cobra venom inhibited the growth of Ehrlich ascites carcinoma (EAC) inoculated subcutaneously in mice. Here, we studied the influence of anti-complementary cobra venom factor (CVF) and the non-steroidal anti-inflammatory drug ketoprofen on the antitumor
[...] Read more.
We showed recently that nerve growth factor (NGF) from cobra venom inhibited the growth of Ehrlich ascites carcinoma (EAC) inoculated subcutaneously in mice. Here, we studied the influence of anti-complementary cobra venom factor (CVF) and the non-steroidal anti-inflammatory drug ketoprofen on the antitumor NGF effect, as well as on NGF-induced changes in EAC histological patterns, the activity of lactate and succinate dehydrogenases in tumor cells and the serum level of some cytokines. NGF, CVF and ketoprofen reduced the tumor volume by approximately 72%, 68% and 30%, respectively. The antitumor effect of NGF was accompanied by an increase in the lymphocytic infiltration of the tumor tissue, the level of interleukin 1β and tumor necrosis factor α in the serum, as well as the activity of lactate and succinate dehydrogenases in tumor cells. Simultaneous administration of NGF with either CVF or ketoprofen abolished the antitumor effect and reduced all other effects of NGF, whereas NGF itself significantly decreased the antitumor action of both CVF and ketoprofen. Thus, the antitumor effect of NGF critically depended on the status of the immune system and was abolished by the disturbance of the complement system; the disturbance of the inflammatory response canceled the antitumor effect as well. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
Figures

Figure 1

Open AccessArticle High Throughput Identification of Antimicrobial Peptides from Fish Gastrointestinal Microbiota
Toxins 2017, 9(9), 266; doi:10.3390/toxins9090266
Received: 10 August 2017 / Revised: 25 August 2017 / Accepted: 28 August 2017 / Published: 30 August 2017
PDF Full-text (10587 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Antimicrobial peptides (AMPs) are a group of small peptides, which are secreted by almost all creatures in nature. They have been explored in therapeutic and agricultural aspects as they are toxic to many bacteria. A considerable amount of work has been conducted in
[...] Read more.
Antimicrobial peptides (AMPs) are a group of small peptides, which are secreted by almost all creatures in nature. They have been explored in therapeutic and agricultural aspects as they are toxic to many bacteria. A considerable amount of work has been conducted in analyzing 16S and metagenomics of the gastrointestinal (GI) microbiome of grass carp (Ctenopharyngodon idellus). However, these datasets are still untapped resources. In this present study, a homologous search was performed to predict AMPs from our newly generated metagenome of grass carp. We identified five AMPs with high similarities to previously reported bacterial toxins, such as lantibiotic and class II bacteriocins. In addition, we observed that the top abundant genus in the GI microbiota of the grass carp was generally consistent with the putative AMP-producing strains, which are mainly from Lactobacillales. Furthermore, we constructed the phylogenetic relationship of these putative AMP-producing bacteria existing in the GI of grass carp and some popular commercial probiotics (commonly used for microecologics), demonstrating that they are closely related. Thus, these strains have the potential to be developed into novel microecologics. In a word, we provide a high-throughput way to discover AMPs from fish GI microbiota, which can be developed as alternative pathogen antagonists (toxins) for microecologics or probiotic supplements. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
Figures

Figure 1

Open AccessFeature PaperArticle Lengths of the C-Terminus and Interconnecting Loops Impact Stability of Spider-Derived Gating Modifier Toxins
Toxins 2017, 9(8), 248; doi:10.3390/toxins9080248
Received: 17 July 2017 / Revised: 8 August 2017 / Accepted: 8 August 2017 / Published: 12 August 2017
PDF Full-text (6638 KB) | HTML Full-text | XML Full-text
Abstract
Spider gating modifier toxins (GMTs) are potent modulators of voltage-gated ion channels and have thus attracted attention as drug leads for several pathophysiological conditions. GMTs contain three disulfide bonds organized in an inhibitory cystine knot, which putatively confers them with high stability; however,
[...] Read more.
Spider gating modifier toxins (GMTs) are potent modulators of voltage-gated ion channels and have thus attracted attention as drug leads for several pathophysiological conditions. GMTs contain three disulfide bonds organized in an inhibitory cystine knot, which putatively confers them with high stability; however, thus far, there has not been a focused study to establish the stability of GMTs in physiological conditions. We examined the resistance of five GMTs including GpTx-1, HnTx-IV, HwTx-IV, PaurTx-3 and SgTx-1, to pH, thermal and proteolytic degradation. The peptides were stable under physiological conditions, except SgTx-1, which was susceptible to proteolysis, probably due to a longer C-terminus compared to the other peptides. In non-physiological conditions, the five peptides withstood chaotropic degradation, and all but SgTx-1 remained intact after prolonged exposure to high temperature; however, the peptides were degraded in strongly alkaline solutions. GpTx-1 and PaurTx-3 were more resistant to basic hydrolysis than HnTx-IV, HwTx-IV and SgTx-1, probably because a shorter interconnecting loop 3 on GpTx-1 and PaurTx-3 may stabilize interactions between the C-terminus and the hydrophobic patch. Here, we establish that most GMTs are exceptionally stable, and propose that, in the design of GMT-based therapeutics, stability can be enhanced by optimizing the C-terminus in terms of length, and increased interactions with the hydrophobic patch. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
Figures

Review

Jump to: Research

Open AccessReview Animal Toxins Providing Insights into TRPV1 Activation Mechanism
Toxins 2017, 9(10), 326; doi:10.3390/toxins9100326
Received: 28 September 2017 / Revised: 13 October 2017 / Accepted: 13 October 2017 / Published: 16 October 2017
PDF Full-text (1715 KB) | HTML Full-text | XML Full-text
Abstract
Beyond providing evolutionary advantages, venoms offer unique research tools, as they were developed to target functionally important proteins and pathways. As a key pain receptor in the nociceptive pathway, transient receptor potential vanilloid 1 (TRPV1) of the TRP superfamily has been shown to
[...] Read more.
Beyond providing evolutionary advantages, venoms offer unique research tools, as they were developed to target functionally important proteins and pathways. As a key pain receptor in the nociceptive pathway, transient receptor potential vanilloid 1 (TRPV1) of the TRP superfamily has been shown to be a target for several toxins, as a way of producing pain to deter predators. Importantly, TRPV1 is involved in thermoregulation, inflammation, and acute nociception. As such, toxins provide tools to understand TRPV1 activation and modulation, a critical step in advancing pain research and the development of novel analgesics. Indeed, the phytotoxin capsaicin, which is the spicy chemical in chili peppers, was invaluable in the original cloning and characterization of TRPV1. The unique properties of each subsequently characterized toxin have continued to advance our understanding of functional, structural, and biophysical characteristics of TRPV1. By building on previous reviews, this work aims to provide a comprehensive summary of the advancements made in TRPV1 research in recent years by employing animal toxins, in particular DkTx, RhTx, BmP01, Echis coloratus toxins, APHCs and HCRG21. We examine each toxin’s functional aspects, behavioral effects, and structural features, all of which have contributed to our current knowledge of TRPV1. We additionally discuss the key features of TRPV1’s outer pore domain, which proves to be the target of the currently discussed toxins. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
Figures

Figure 1

Open AccessReview Botulinum Toxin for the Treatment of Neuropathic Pain
Toxins 2017, 9(9), 260; doi:10.3390/toxins9090260
Received: 10 August 2017 / Revised: 18 August 2017 / Accepted: 21 August 2017 / Published: 24 August 2017
PDF Full-text (638 KB) | HTML Full-text | XML Full-text
Abstract
Botulinum toxin (BoNT) has been used as a treatment for excessive muscle stiffness, spasticity, and dystonia. BoNT for approximately 40 years, and has recently been used to treat various types of neuropathic pain. The mechanism by which BoNT acts on neuropathic pain involves
[...] Read more.
Botulinum toxin (BoNT) has been used as a treatment for excessive muscle stiffness, spasticity, and dystonia. BoNT for approximately 40 years, and has recently been used to treat various types of neuropathic pain. The mechanism by which BoNT acts on neuropathic pain involves inhibiting the release of inflammatory mediators and peripheral neurotransmitters from sensory nerves. Recent journals have demonstrated that BoNT is effective for neuropathic pain, such as postherpetic neuralgia, trigeminal neuralgia, and peripheral neuralgia. The purpose of this review is to summarize the experimental and clinical evidence of the mechanism by which BoNT acts on various types of neuropathic pain and describe why BoNT can be applied as treatment. The PubMed database was searched from 1988 to May 2017. Recent studies have demonstrated that BoNT injections are effective treatments for post-herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia, and intractable neuropathic pain, such as poststroke pain and spinal cord injury. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
Figures

Figure 1

Journal Contact

MDPI AG
Toxins Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
E-Mail: 
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Toxins Edit a special issue Review for Toxins
logo
loading...
Back to Top