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Marine Drugs
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Ion Channels as Marine Drug Targets
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Ion Channels as Marine Drug Targets

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (30 October 2020) | Viewed by 32332

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Jean-Marc Sabatier

E-Mail Website
Guest Editor
Institute of Neurophysiopathology (INP), Aix-Marseille University, Faculté des sciences médicales et paramédicales, 27, Bd Jean Moulin, 13005 Marseille, France
Interests: antimicrobial peptides; antibacterial; antibiotics; structure-activity relationships; bacteriocins; drug design; peptide engineering
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Animal venoms, especially of marine origin, are rich natural sources of bioactive compounds. The molecular targets of the latter are mainly ion (i.e., sodium, potassium, calcium, and chloride) channels with their numerous variants/subtypes. These venom molecules are exhibiting diverse potencies and selectivities and may have some therapeutic potential based on their cellular targets. Over the past decade, marine molecules have been widely studied, as they represent potential drugs to treat a variety of (human) pathologies, from pain to autoimmune and neurological diseases. This Special Issue of “Marine Drugs” is devoted to the different aspects of the marine (or marine-derived) molecules, from the discovery and structural characterization to the pharmacology and molecular engineering in order to finally develop some “novel” candidate chemotherapeutic drugs targeting the ion channel(s).

Dr. Jean-Marc Sabatier
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 submissions that pass pre-check are 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. Marine Drugs 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 2900 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

  • ion channel
  • immunomodulator
  • pain killer
  • candidate drug
  • marine drug
  • structure-activity relationships
  • venomous marine animal
  • animal venom
  • toxin
  • sea snake
  • sea anemone
  • jellyfish
  • stingray
  • puffer fish
  • scorpion fish
  • marine cone snail

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Related Special Issues

Published Papers (7 papers)

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Research

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11 pages, 895 KiB  
Article
Botulinum Toxin-Chitosan Nanoparticles Prevent Arrhythmia in Experimental Rat Models
by David Sergeevichev, Vladislav Fomenko, Artem Strelnikov, Anna Dokuchaeva, Maria Vasilieva, Elena Chepeleva, Yanina Rusakova, Sergey Artemenko, Alexander Romanov, Nariman Salakhutdinov and Alexander Chernyavskiy
Mar. Drugs 2020, 18(8), 410; https://doi.org/10.3390/md18080410 - 2 Aug 2020
Cited by 8 | Viewed by 3759
Abstract
Several experimental studies have recently demonstrated that temporary autonomic block using botulinum toxin (BoNT/A1) might be a novel option for the treatment of atrial fibrillation. However, the assessment of antiarrhythmic properties of BoNT has so far been limited, relying exclusively on vagal stimulation [...] Read more.
Several experimental studies have recently demonstrated that temporary autonomic block using botulinum toxin (BoNT/A1) might be a novel option for the treatment of atrial fibrillation. However, the assessment of antiarrhythmic properties of BoNT has so far been limited, relying exclusively on vagal stimulation and rapid atrial pacing models. The present study examined the antiarrhythmic effect of specially formulated BoNT/A1-chitosan nanoparticles (BTN) in calcium chloride-, barium chloride- and electrically induced arrhythmia rat models. BTN enhanced the effect of BoNT/A1. Subepicardial injection of BTN resulted in a significant antiarrhythmic effect in investigated rat models. BTN formulation antagonizes arrhythmia induced by the activation of Ca, K and Na channels. Full article
(This article belongs to the Special Issue Ion Channels as Marine Drug Targets)
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13 pages, 3144 KiB  
Article
Characterisation of δ-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator
by Dan Wang, S.W.A. Himaya, Jean Giacomotto, Md. Mahadhi Hasan, Fernanda C. Cardoso, Lotten Ragnarsson and Richard J. Lewis
Mar. Drugs 2020, 18(7), 343; https://doi.org/10.3390/md18070343 - 30 Jun 2020
Cited by 4 | Viewed by 3214
Abstract
The 27-amino acid (aa)-long δ-conotoxin TxVIA, originally isolated from the mollusc-hunting cone snail Conus textile, slows voltage-gated sodium (NaV) channel inactivation in molluscan neurons, but its mammalian ion channel targets remain undetermined. In this study, we confirmed that TxVIA was [...] Read more.
The 27-amino acid (aa)-long δ-conotoxin TxVIA, originally isolated from the mollusc-hunting cone snail Conus textile, slows voltage-gated sodium (NaV) channel inactivation in molluscan neurons, but its mammalian ion channel targets remain undetermined. In this study, we confirmed that TxVIA was inactive on mammalian NaV1.2 and NaV1.7 even at high concentrations (10 µM). Given the fact that invertebrate NaV channel and T-type calcium channels (CaV3.x) are evolutionarily related, we examined the possibility that TxVIA may act on CaV3.x. Electrophysiological characterisation of the native TxVIA on CaV3.1, 3.2 and 3.3 revealed that TxVIA preferentially inhibits CaV3.2 current (IC50 = 0.24 μM) and enhances CaV3.1 current at higher concentrations. In fish bioassays TxVIA showed little effect on zebrafish behaviours when injected intramuscular at 250 ng/100 mg fish. The binding sites for TxVIA at NaV1.7 and CaV3.1 revealed that their channel binding sites contained a common epitope. Full article
(This article belongs to the Special Issue Ion Channels as Marine Drug Targets)
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15 pages, 1469 KiB  
Article
RgIA4 Accelerates Recovery from Paclitaxel-Induced Neuropathic Pain in Rats
by Peter N. Huynh, Denise Giuvelis, Sean Christensen, Kerry L. Tucker and J. Michael McIntosh
Mar. Drugs 2020, 18(1), 12; https://doi.org/10.3390/md18010012 - 21 Dec 2019
Cited by 29 | Viewed by 4454
Abstract
Chemotherapeutic drugs are widely utilized in the treatment of human cancers. Painful chemotherapy-induced neuropathy is a common, debilitating, and dose-limiting side effect for which there is currently no effective treatment. Previous studies have demonstrated the potential utility of peptides from the marine snail [...] Read more.
Chemotherapeutic drugs are widely utilized in the treatment of human cancers. Painful chemotherapy-induced neuropathy is a common, debilitating, and dose-limiting side effect for which there is currently no effective treatment. Previous studies have demonstrated the potential utility of peptides from the marine snail from the genus Conus for the treatment of neuropathic pain. α-Conotoxin RgIA and a potent analog, RgIA4, have previously been shown to prevent the development of neuropathy resulting from the administration of oxaliplatin, a platinum-based antineoplastic drug. Here, we have examined its efficacy against paclitaxel, a chemotherapeutic drug that works by a mechanism of action distinct from that of oxaliplatin. Paclitaxel was administered at 2 mg/kg (intraperitoneally (IP)) every other day for a total of 8 mg/kg. Sprague Dawley rats that were co-administered RgIA4 at 80 µg/kg (subcutaneously (SC)) once daily, five times per week, for three weeks showed significant recovery from mechanical allodynia by day 31. Notably, the therapeutic effects reached significance 12 days after the last administration of RgIA4, which is suggestive of a rescue mechanism. These findings support the effects of RgIA4 in multiple chemotherapeutic models and the investigation of α9α10 nicotinic acetylcholine receptors (nAChRs) as a non-opioid target in the treatment of chronic pain. Full article
(This article belongs to the Special Issue Ion Channels as Marine Drug Targets)
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18 pages, 2085 KiB  
Article
Venomics Reveals Venom Complexity of the Piscivorous Cone Snail, Conus tulipa
by Mriga Dutt, Sébastien Dutertre, Ai-Hua Jin, Vincent Lavergne, Paul Francis Alewood and Richard James Lewis
Mar. Drugs 2019, 17(1), 71; https://doi.org/10.3390/md17010071 - 21 Jan 2019
Cited by 19 | Viewed by 5262
Abstract
The piscivorous cone snail Conus tulipa has evolved a net-hunting strategy, akin to the deadly Conus geographus, and is considered the second most dangerous cone snail to humans. Here, we present the first venomics study of C. tulipa venom using integrated transcriptomic [...] Read more.
The piscivorous cone snail Conus tulipa has evolved a net-hunting strategy, akin to the deadly Conus geographus, and is considered the second most dangerous cone snail to humans. Here, we present the first venomics study of C. tulipa venom using integrated transcriptomic and proteomic approaches. Parallel transcriptomic analysis of two C. tulipa specimens revealed striking differences in conopeptide expression levels (2.5-fold) between individuals, identifying 522 and 328 conotoxin precursors from 18 known gene superfamilies. Despite broad overlap at the superfamily level, only 86 precursors (11%) were common to both specimens. Conantokins (NMDA antagonists) from the superfamily B1 dominated the transcriptome and proteome of C. tulipa venom, along with superfamilies B2, A, O1, O3, con-ikot-ikot and conopressins, plus novel putative conotoxins precursors T1.3, T6.2, T6.3, T6.4 and T8.1. Thus, C. tulipa venom comprised both paralytic (putative ion channel modulating α-, ω-, μ-, δ-) and non-paralytic (conantokins, con-ikot-ikots, conopressins) conotoxins. This venomic study confirms the potential for non-paralytic conotoxins to contribute to the net-hunting strategy of C. tulipa. Full article
(This article belongs to the Special Issue Ion Channels as Marine Drug Targets)
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Review

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28 pages, 2406 KiB  
Review
Marine Toxins Targeting Kv1 Channels: Pharmacological Tools and Therapeutic Scaffolds
by Rocio K. Finol-Urdaneta, Aleksandra Belovanovic, Milica Micic-Vicovac, Gemma K. Kinsella, Jeffrey R. McArthur and Ahmed Al-Sabi
Mar. Drugs 2020, 18(3), 173; https://doi.org/10.3390/md18030173 - 20 Mar 2020
Cited by 35 | Viewed by 5798
Abstract
Toxins from marine animals provide molecular tools for the study of many ion channels, including mammalian voltage-gated potassium channels of the Kv1 family. Selectivity profiling and molecular investigation of these toxins have contributed to the development of novel drug leads with therapeutic potential [...] Read more.
Toxins from marine animals provide molecular tools for the study of many ion channels, including mammalian voltage-gated potassium channels of the Kv1 family. Selectivity profiling and molecular investigation of these toxins have contributed to the development of novel drug leads with therapeutic potential for the treatment of ion channel-related diseases or channelopathies. Here, we review specific peptide and small-molecule marine toxins modulating Kv1 channels and thus cover recent findings of bioactives found in the venoms of marine Gastropod (cone snails), Cnidarian (sea anemones), and small compounds from cyanobacteria. Furthermore, we discuss pivotal advancements at exploiting the interaction of κM-conotoxin RIIIJ and heteromeric Kv1.1/1.2 channels as prevalent neuronal Kv complex. RIIIJ’s exquisite Kv1 subtype selectivity underpins a novel and facile functional classification of large-diameter dorsal root ganglion neurons. The vast potential of marine toxins warrants further collaborative efforts and high-throughput approaches aimed at the discovery and profiling of Kv1-targeted bioactives, which will greatly accelerate the development of a thorough molecular toolbox and much-needed therapeutics. Full article
(This article belongs to the Special Issue Ion Channels as Marine Drug Targets)
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19 pages, 7628 KiB  
Review
Synthetic Approaches to Zetekitoxin AB, a Potent Voltage-Gated Sodium Channel Inhibitor
by Kanna Adachi, Hayate Ishizuka, Minami Odagi and Kazuo Nagasawa
Mar. Drugs 2020, 18(1), 24; https://doi.org/10.3390/md18010024 - 26 Dec 2019
Cited by 7 | Viewed by 4542
Abstract
Voltage-gated sodium channels (NaVs) are membrane proteins that are involved in the generation and propagation of action potentials in neurons. Recently, the structure of a complex made of a tetrodotoxin-sensitive (TTX-s) NaV subtype with saxitoxin (STX), a shellfish toxin, was [...] Read more.
Voltage-gated sodium channels (NaVs) are membrane proteins that are involved in the generation and propagation of action potentials in neurons. Recently, the structure of a complex made of a tetrodotoxin-sensitive (TTX-s) NaV subtype with saxitoxin (STX), a shellfish toxin, was determined. STX potently inhibits TTX-s NaV, and is used as a biological tool to investigate the function of NaVs. More than 50 analogs of STX have been isolated from nature. Among them, zetekitoxin AB (ZTX) has a distinctive chemical structure, and is the most potent inhibitor of NaVs, including tetrodotoxin-resistant (TTX-r) NaV. Despite intensive synthetic studies, total synthesis of ZTX has not yet been achieved. Here, we review recent efforts directed toward the total synthesis of ZTX, including syntheses of 11-saxitoxinethanoic acid (SEA), which is considered a useful synthetic model for ZTX, since it contains a key carbon–carbon bond at the C11 position. Full article
(This article belongs to the Special Issue Ion Channels as Marine Drug Targets)
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13 pages, 1689 KiB  
Review
Marine Natural Products and Drug Resistance in Latent Tuberculosis
by Muhammad Tahir Khan, Aman Chandra Kaushik, Aamer Iqbal Bhatti, Yu-Juan Zhang, Shulin Zhang, Amie Jinghua Wei, Shaukat Iqbal Malik and Dong Qing Wei
Mar. Drugs 2019, 17(10), 549; https://doi.org/10.3390/md17100549 - 26 Sep 2019
Cited by 13 | Viewed by 4090
Abstract
Pyrazinamide (PZA) is the only drug for the elimination of latent Mycobacterium tuberculosis (MTB) isolates. However, due to the increased number of PZA-resistance, the chances of the success of global TB elimination seems to be more prolonged. Recently, marine natural products (MNPs) as [...] Read more.
Pyrazinamide (PZA) is the only drug for the elimination of latent Mycobacterium tuberculosis (MTB) isolates. However, due to the increased number of PZA-resistance, the chances of the success of global TB elimination seems to be more prolonged. Recently, marine natural products (MNPs) as an anti-TB agent have received much attention, where some compounds extracted from marine sponge, Haliclona sp. exhibited strong activity under aerobic and hypoxic conditions. In this study, we screened articles from 1994 to 2019 related to marine natural products (MNPs) active against latent MTB isolates. The literature was also mined for the major regulators to map them in the form of a pathway under the dormant stage. Five compounds were found to be more suitable that may be applied as an alternative to PZA for the better management of resistance under latent stage. However, the mechanism of actions behind these compounds is largely unknown. Here, we also applied synthetic biology to analyze the major regulatory pathway under latent TB that might be used for the screening of selective inhibitors among marine natural products (MNPs). We identified key regulators of MTB under latent TB through extensive literature mining and mapped them in the form of regulatory pathway, where SigH is negatively regulated by RshA. PknB, RshA, SigH, and RNA polymerase (RNA-pol) are the major regulators involved in MTB survival under latent stage. Further studies are needed to screen MNPs active against the main regulators of dormant MTB isolates. To reduce the PZA resistance burden, understanding the regulatory pathways may help in selective targets of MNPs from marine natural sources. Full article
(This article belongs to the Special Issue Ion Channels as Marine Drug Targets)
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