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Special Issue "Molecular Mechanisms of Animal Toxins, Venoms and Antivenoms"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: 28 February 2023 | Viewed by 2582

Special Issue Editors

Prof. Dr. R. Manjunatha Kini
E-Mail Website
Guest Editor
Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore
Interests: protein chemistry; structure-function relationships; protein–protein interaction; protein design and engineering

Special Issue Information

Dear Colleagues,

In some animals, venoms have appeared as a means of defense and/or as a means of attack/hunting. Venoms may contain components of various chemical nature, commonly referred to as toxins. In the course of evolution, toxins have acquired the ability to selectively and effectively affect certain systems in the organism of the victim or predator. The development of methods for the identification and analysis of the chemical structure of organic compounds leads to the discovery of new toxins, for which it is necessary to establish the mechanisms of action. Moreover, new species of venomous animals are being discovered, for which it is also necessary to establish the molecular mechanisms of venom action. This understanding is very important for the effective treatment of intoxications, which still remain a serious problem in a number of regions of the planet. Currently, the most effective way to treat bites of venomous animals is the use of antisera obtained by immunizing large mammals (mainly horses) with small doses of venom. Although very effective, this method has a number of disadvantages, which requires the development of new treatments based on other molecular mechanisms. Since toxins are highly efficacious and selective for certain biological targets, they can serve as templates for drug development. Thus, the study of the molecular mechanisms of action of animal venoms, their toxins and new antitoxins is a very important task. The purpose of this Special Issue is to present the state of the art in the study of the molecular mechanisms underlying the action of animal venoms, their components and antitoxins.

Research articles, review articles as well as short communications are invited.

Please note that, for IJMS papers, theoretical studies should offer new insights into the understanding of experimental results or suggest new experimentally testable hypotheses

Prof. Dr. R. Manjunatha Kini
Prof. Dr. Yuri N. Utkin
Guest Editors

Manuscript Submission Information

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • venom
  • toxin
  • antitoxin
  • antivenom
  • neurotoxin
  • cytotoxin
  • hemotoxin
  • conotoxin
  • snake
  • scorpion
  • spider

Published Papers (4 papers)

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Research

Article
Characterization of the First Animal Toxin Acting as an Antagonist on AT1 Receptor
Int. J. Mol. Sci. 2023, 24(3), 2330; https://doi.org/10.3390/ijms24032330 - 24 Jan 2023
Viewed by 336
Abstract
The renin-angiotensin system (RAS) is one of the main regulatory systems of cardiovascular homeostasis. It is mainly composed of angiotensin-converting enzyme (ACE) and angiotensin II receptors AT1 and AT2. ACE and AT1 are targets of choice for the treatment of hypertension, whereas the [...] Read more.
The renin-angiotensin system (RAS) is one of the main regulatory systems of cardiovascular homeostasis. It is mainly composed of angiotensin-converting enzyme (ACE) and angiotensin II receptors AT1 and AT2. ACE and AT1 are targets of choice for the treatment of hypertension, whereas the AT2 receptor is still not exploited due to the lack of knowledge of its physiological properties. Peptide toxins from venoms display multiple biological functions associated with varied chemical and structural properties. If Brazilian viper toxins have been described to inhibit ACE, no animal toxin is known to act on AT1/AT2 receptors. We screened a library of toxins on angiotensin II receptors with a radioligand competition binding assay. Functional characterization of the selected toxin was conducted by measuring second messenger production, G-protein activation and β-arrestin 2 recruitment using bioluminescence resonance energy transfer (BRET) based biosensors. We identified one original toxin, A-CTX-cMila, which is a 7-residues cyclic peptide from Conus miliaris with no homology sequence with known angiotensin peptides nor identified toxins, displaying a 100-fold selectivity for AT1 over AT2. This toxin shows a competitive antagonism mode of action on AT1, blocking Gαq, Gαi3, GαoA, β-arrestin 2 pathways and ERK1/2 activation. These results describe the first animal toxin active on angiotensin II receptors. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Animal Toxins, Venoms and Antivenoms)
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Article
Complement System Inhibition Modulates the Inflammation Induced by the Venom of Premolis semirufa, an Amazon Rainforest Moth Caterpillar
Int. J. Mol. Sci. 2022, 23(21), 13333; https://doi.org/10.3390/ijms232113333 - 01 Nov 2022
Viewed by 544
Abstract
The caterpillar of the Premolis semirufa moth, commonly called Pararama, is found in the Brazilian Amazon region. Contact with the hairs can cause a chronic inflammatory reaction, termed “pararamosis”. To date, there is still no specific treatment for pararamosis. In this study, we [...] Read more.
The caterpillar of the Premolis semirufa moth, commonly called Pararama, is found in the Brazilian Amazon region. Contact with the hairs can cause a chronic inflammatory reaction, termed “pararamosis”. To date, there is still no specific treatment for pararamosis. In this study, we used a whole human blood model to evaluate the involvement of the complement in the proinflammatory effects of P. semirufa hair extract, as well as the anti-inflammatory potential of complement inhibitors in this process. After treatment of blood samples with the P. semirufa hair extract, there was a significant increase in the generation of soluble terminal complement complex (sTCC) and anaphylatoxins (C3a, C4a, and C5a), as well as the production of the cytokines TNF-α and IL-17 and the chemokines IL-8, RANTES, MIG, MCP-1, and IP-10. The inhibition of C3 with compstatin significantly decreased IL-17, IL-8, RANTES, and MCP-1 production. However, the use of the C5aR1 antagonist PMX205 promoted a reduction in the production of IL-8 and RANTES. Moreover, compstatin decreased CD11b, C5aR1, and TLR2 expression induced by P. semirufa hair extract in granulocytes and CD11b, TLR4, and TLR2 in monocytes. When we incubated vascular endothelial cells with extract-treated human plasma, there was an increase in IL-8 and MCP-1 production, and compstatin was able to decrease the production of these chemokines. C5aR1 antagonism also decreased the production of MCP-1 in endothelial cells. Thus, these results indicate that the extract of the Pararama bristles activates the complement system and that this action contributes to the production of cytokines and chemokines, modulation of the expression of surface markers in leukocytes, and activation of endothelial cells. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Animal Toxins, Venoms and Antivenoms)
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Article
The Deadly Toxin Arsenal of the Tree-Dwelling Australian Funnel-Web Spiders
Int. J. Mol. Sci. 2022, 23(21), 13077; https://doi.org/10.3390/ijms232113077 - 28 Oct 2022
Viewed by 787
Abstract
Australian funnel-web spiders are amongst the most dangerous venomous animals. Their venoms induce potentially deadly symptoms, including hyper- and hypotension, tachycardia, bradycardia and pulmonary oedema. Human envenomation is more frequent with the ground-dwelling species, including the infamous Sydney funnel-web spider (Atrax robustus [...] Read more.
Australian funnel-web spiders are amongst the most dangerous venomous animals. Their venoms induce potentially deadly symptoms, including hyper- and hypotension, tachycardia, bradycardia and pulmonary oedema. Human envenomation is more frequent with the ground-dwelling species, including the infamous Sydney funnel-web spider (Atrax robustus); although, only two tree-dwelling species induce more severe envenomation. To unravel the mechanisms that lead to this stark difference in clinical outcomes, we investigated the venom transcriptome and proteome of arboreal Hadronyche cerberea and H. formidabilis. Overall, Hadronyche venoms comprised 44 toxin superfamilies, with 12 being exclusive to tree-dwellers. Surprisingly, the major venom components were neprilysins and uncharacterized peptides, in addition to the well-known ω- and δ-hexatoxins and double-knot peptides. The insecticidal effects of Hadronyche venom on sheep blowflies were more potent than Atrax venom, and the venom of both tree- and ground-dwelling species potently modulated human voltage-gated sodium channels, particularly NaV1.2. Only the venom of tree-dwellers exhibited potent modulation of voltage-gated calcium channels. H. formidabilis appeared to be under less diversifying selection pressure compared to the newly adapted tree-dweller, H. cerberea. Thus, this study contributes to unravelling the fascinating molecular and pharmacological basis for the severe envenomation caused by the Australian tree-dwelling funnel-web spiders. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Animal Toxins, Venoms and Antivenoms)
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Article
Rat Group IIA Secreted Phospholipase A2 Binds to Cytochrome c Oxidase and Inhibits Its Activity: A Possible Episode in the Development of Alzheimer’s Disease
Int. J. Mol. Sci. 2022, 23(20), 12368; https://doi.org/10.3390/ijms232012368 - 15 Oct 2022
Viewed by 593
Abstract
Alzheimer’s disease (AD), a progressive form of dementia, is characterized by the increased expression of secreted phospholipase A2 group IIA (GIIA) in the affected tissue and the dysfunction of neuronal mitochondria, similar to that induced by an orthologous GIIA from snake venom, [...] Read more.
Alzheimer’s disease (AD), a progressive form of dementia, is characterized by the increased expression of secreted phospholipase A2 group IIA (GIIA) in the affected tissue and the dysfunction of neuronal mitochondria, similar to that induced by an orthologous GIIA from snake venom, β-neurotoxic ammodytoxin (Atx), in the motor neurons. To advance our knowledge about the role of GIIA in AD, we studied the effect of rat GIIA on the neuronal mitochondria and compared it with that of the Atx. We produced recombinant rat GIIA (rGIIA) and its enzymatically inactive mutant, rGIIA(D49S), and demonstrated that they interact with the subunit II of cytochrome c oxidase (CCOX-II) as Atx. rGIIA and rGIIA(D49S) bound to this essential constituent of the respiratory chain complex with an approximately 100-fold lower affinity than Atx; nevertheless, both rGIIA molecules potently inhibited the CCOX activity in the isolated rat mitochondria. Like Atx, rGIIA was able to reach the mitochondria in the PC12 cells from the extracellular space, independent of its enzymatic activity. Consistently, the inhibition of the CCOX activity in the intact PC12 cells and in the rat’s brain tissue sections was clearly demonstrated using rGIIA(D49S). Our results show that the effects of mammalian and snake venom β-neurotoxic GIIA on the neuronal mitochondria have similar molecular backgrounds. They suggest that the elevated extracellular concentration of GIIA in the AD tissue drives the translocation of this enzyme into local neurons and their mitochondria to inhibit the activity of the CCOX in the respiratory chain. Consequently, the process of oxidative phosphorylation in the neurons is attenuated, eventually leading to their degeneration. Atx was thus revealed as a valuable molecular tool for further investigations of the role of GIIA in AD. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Animal Toxins, Venoms and Antivenoms)
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