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The occurrence of antibiotic-resistant bacteria is a serious global health issue, and it emphasizes the need for novel antimicrobial agents. This review explores the potential of snake venom as another alternative strategy against antimicrobial resistance. Snake venoms are complex combinations of bioactive peptides and proteins, including metalloproteases (MPs), serine proteases (SPs), phospholipase A2 (PLA2) enzymes, three-finger toxins (3FTXs), cysteine-rich secretory proteins (CRISPs), L-amino acid oxidases (LAAOs), and antimicrobial peptides (AMPs). The antibacterial products possess wide-spectrum antibacterial activity against resistant microbes via diverse mechanisms such as cell membrane disruption, enzymatic hydrolysis of microbial structures, generation of oxidative stress, inhibition of biofilms, and immunomodulation. Strong antimicrobial activity is reported by most studies, but these are mostly restricted to in vitro testing with low translational use. Although preliminary insights into molecular targets and physiological effects exist, further studies are needed to clarify long-term safety and therapeutic potential. Special attention is given to snake venom-derived extracellular vesicles (SVEVs), which enhance the therapeutic potential of venom toxins by protecting them from degradation, improving bioavailability, and facilitating targeted delivery. Furthermore, innovative delivery strategies such as PEGylation, liposomes, hydrogels, microneedle patches, biopolymer films, and nanoparticles are discussed for their role in reducing systemic toxicity and enhancing antimicrobial efficacy. The rational modification of venom-derived peptides further expands their therapeutic utility by improving pharmacokinetics and minimizing off-target effects. Together, these approaches highlight the translational potential of snake venom-based therapies as next-generation antimicrobials in the fight against resistant infections. By outlining these challenges and directions, this review positions snake venom as an overlooked but fertile resource in the battle against antibiotic resistance.

Scorpion venom are composed mainly of bioactive proteins and peptides that may serve as lead compounds for the design of biotechnological tools and therapeutic drugs. However, exploring the therapeutic potential of scorpion venom components is mainly impaired by the low yield of purified toxins from milked venom. Therefore, production of toxin-derived peptides and proteins by heterologous expression is the strategy of choice for research groups and pharmaceutical industry to overcome this limitation. Recombinant expression in microorganisms is often the first choice, since bacteria and yeast systems combine high level of recombinant protein expression, fast cell growth and multiplication and simple media requirement. Herein, we present a comprehensive revision, which describes the scorpion venom components that were produced in their recombinant forms using microbial systems. In addition, we highlight the pros and cons of performing the heterologous expression of these compounds, regarding the particularities of each microorganism and how these processes can affect the application of these venom components. The most used microbial system in the heterologous expression of scorpion venom components is Escherichia coli (85%), and among all the recombinant venom components produced, 69% were neurotoxins. This review may light up future researchers in the choice of the best expression system to produce scorpion venom components of interest.

The Tityus serrulatus scorpion is considered the most dangerous of the Brazilian fauna due to the severe clinical manifestations in injured victims. Despite being abundant components of the venom, few linear peptides have been characterized so far, such as hypotensins. In vivo studies have demonstrated that hypotensin I (TsHpt-I) exerts hypotensive activity, with an angiotensin-converting enzyme (ACE)-independent mechanism of action. Since experiments have not yet been carried out to analyze the direct interaction of hypotensins with ACE, and to deepen the knowledge about these peptides, hypotensins I and II (TsHpt-II) were studied regarding their modulatory action over the activities of ACE and neprilysin (NEP), which are the peptidases involved in blood pressure control. Aiming to search for indications of possible pro-inflammatory action, hypotensins were also analyzed for their role in murine macrophage viability, the release of interleukins and phagocytic activity. TsHpt-I and -II were used in kinetic studies with the metallopeptidases ACE and NEP, and both hypotensins were able to increase the activity of ACE. TsHpt-I presented itself as an inhibitor of NEP, whereas TsHpt-II showed weak inhibition of the enzyme. The mechanism of inhibition of TsHpt-I in relation to NEP was defined as non-competitive, with an inhibition constant (Ki) of 4.35 μM. Concerning the analysis of cell viability and modulation of interleukin levels and phagocytic activity, BALB/c mice’s naïve macrophages were used, and an increase in TNF production in the presence of TsHpt-I and -II was observed, as well as an increase in IL-6 production in the presence of TsHpt-II only. Both hypotensins were able to increase the phagocytic activity of murine macrophages in vitro. The difference between TsHpt-I and -II is the residue at position 15, with a glutamine in TsHpt-I and a glutamic acid in TsHpt-II. Despite this, kinetic analyzes and cell assays indicated different actions of TsHpt-I and -II. Taken together, these results suggest a new mechanism for the hypotensive effects of TsHpt-I and -II. Furthermore, the release of some interleukins also suggests a role for these peptides in the venom inflammatory response. Even though these molecules have been well studied, the present results suggest a new mechanism for the hypotensive effects of TsHpt-I

Background: Most of insecticides target sodium channels. The increasing emergence of resistance to these insecticides has caused researchers to look for alternative compounds that. Scorpion venom gland as a reservoir of potent components which selectively target insect sodium channels is a good source for this purpose.Methods: Transcriptome of venom gland of scorpion, Mesobuthus eupeuswas gotten using RNA extraction and cDNA library synthesis. Obtained transcriptome were blasted against proteins databases to find insect sodium channel toxins based on homology.Physicochemical propertiesof an identified protein were calculated using bioinformatics software. Three-dimensional structure of this protein was determined using homology modelling and the final structure was assessed by MD simulation.Results: We found a sodium channel blocker in the transcriptome of M. eupeus venom gland and submitted it in the GenBank under the name of meuNa10. meuNa10 is a stable hydrophilic protein composed of 69 amino acids with the molecular weight of 7721.77 g/mol and pI of 8.7. The tertiary structure of this protein revealed a conserved CS-alpha/b eta domain stabilizing with the help of eight cysteine residues. meuNa10 is also classified as a member of the 3FP family due to containing the finger-like three beta strands.Conclusion:Conclusively, being specific to insect sodium channel along with suitable physicochemical properties including being small, stable, and water-soluble make meuNa10 a good candidate for further in vivo and in vitro experiments to develop a new bioinsecticide.

Scorpion venom is a rich source of biological active peptides and proteins. Transcriptome analysis of the venom gland provides detailed insights about peptide and protein venom components. Following the transcriptome analysis of different species in our previous studies, our research team has focused on the as one of the endemic scorpions of Iran to obtain information about its venom proteins, in order to develop biological research focusing on medicinal applications of scorpion venom components and antivenom production. To gain insights into the protein composition of this scorpion venom, we performed transcriptomic analysis. Transcriptomic analysis of the venom gland of H. prepared from the Khuzestan province, was performed through Illumina paired-end sequencing (RNA-Seq), Trinity assembly, CD-Hit-EST clustering, and annotation of identified primary structures using bioinformatics approaches. Transcriptome analysis showed the presence of 96.4% of complete arthropod BUSCOs, indicating a high-quality assembly. From total of 45,795,108 paired-end 150 bp trimmed reads, the clustering step resulted in the generation of 101,180 assembled transcripts with N size of 1,149 bp. 96,071 Unigenes and 131,235 transcripts had a significant similarity (E-value 1e-3) with known proteins from UniProt, Swissprot, Animal toxin annotation project, and the Pfam database. The results were validated using InterProScan. These mainly correspond to ion channel inhibitors, metalloproteinases, neurotoxins, protease inhibitors, protease activators, Cysteine-rich secretory proteins, phospholipase A enzymes, antimicrobial peptides, growth factors, lipolysis-activating peptides, hyaluronidase, and, phospholipase D. Our venom gland transcriptomic approach identified several biologically active peptides including five LVP1-alpha and LVP1-beta isoforms, which we named HzLVP1_alpha1, HzLVP1_alpha2, HzLVP1_alpha3, HzLVP1_beta1, and HzLVP1_beta and have extremely characterized here. Except for HzLVP1_beta1, all other identified LVP1s are predicted to be stable proteins (instability index <40). Moreover, all isoform of LVP1s alpha and beta subunits are thermostable, with the most stability for HzLVP1_alpha2 (aliphatic index = 71.38). HzLVP1_alpha2 has also the highest half-life. Three-dimensional structure of all identified proteins compacts with three disulfide bridges. The extra cysteine residue may allow the proteins to form a hetero- or homodimer. LVP1 subunits of potentially interact with adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), two key enzymes in regulation of lipolysis in adipocytes, suggesting pharmacological properties of these identified proteins.

Bee venom is a natural toxin produced by honeybees and plays an important role in defending bee colonies. Bee venom has several kinds of peptides, including melittin, apamin, adolapamine, and mast cell degranulation peptides. Apamin accounts for about 2%–3% dry weight of bee venom and is a peptide neurotoxin that contains 18 amino acid residues that are tightly crosslinked by two disulfide bonds. It is well known for its pharmacological functions, which irreversibly block Ca2+-activated K+ (SK) channels. Apamin regulates gene expression in various signal transduction pathways involved in cell development. The aim of this study was to review the current understanding of apamin in the treatment of apoptosis, fibrosis, and central nervous system diseases, which are the pathological processes of various diseases. Apamin’s potential therapeutic and pharmacological applications are also discussed.

In many cases of envenoming following snake bite, the snake responsible for the accident remains unidentified; this frequently results in difficulty deciding which antivenom to administer to the systemically-envenomed victim, especially when only monospecific antivenoms are available. Normally the specific diagnosis of snake bite can be conveniently made using clinical and laboratory methods. Where clinical diagnosis depends upon the recognition of specific signs of envenoming in the patient, laboratory diagnosis is based on the changes which occur in envenomed victims including the detection of abnormalities in blood parameters, presence/absence of myoglobinuria, changes in certain enzyme levels, presence/absence of neurotoxic signs and the detection in the blood of specific venom antigens using immunologically-based techniques, such as enzyme immunoassay. It is the latter which is the main subject of this review, together with the application of techniques currently used to objectively assess the effectiveness of new and existing antivenoms, to assess first aid measures, to investigate the possible use of such methods in epidemiological studies, and to detect individual venom components. With this in mind, we have discussed in some detail how such techniques were developed and how they have helped in the treatment of envenoming particularly and in venom research in general.

Background Snake venoms are trophic adaptations that represent an ideal model to examine the evolutionary factors that shape polymorphic traits under strong natural selection. Venom compositional variation is substantial within and among venomous snake species. However, the forces shaping this phenotypic complexity, as well as the potential integrated roles of biotic and abiotic factors, have received little attention. Here, we investigate geographic variation in venom composition in a wide-ranging rattlesnake ( Crotalus viridis viridis ) and contextualize this variation by investigating dietary, phylogenetic, and environmental variables that covary with venom. Results Using shotgun proteomics, venom biochemical profiling, and lethality assays, we identify 2 distinct divergent phenotypes that characterize major axes of venom variation in this species: a myotoxin-rich phenotype and a snake venom metalloprotease (SVMP)-rich phenotype. We find that dietary availability and temperature-related abiotic factors are correlated with geographic trends in venom composition. Conclusions Our findings highlight the potential for snake venoms to vary extensively within species, for this variation to be driven by biotic and abiotic factors, and for the importance of integrating biotic and abiotic variation for understanding complex trait evolution. Links between venom variation and variation in biotic and abiotic factors indicate that venom variation likely results from substantial geographic variation in selection regimes that determine the efficacy of venom phenotypes across populations and snake species. Our results highlight the cascading influence of abiotic factors on biotic factors that ultimately shape venom phenotype, providing evidence for a central role of local selection as a key driver of venom variation.

Sea anemones produce venoms of exceptional molecular diversity, with at least 17 different molecular scaffolds reported to date. These venom components have traditionally been classified according to pharmacological activity and amino acid sequence. However, this classification system suffers from vulnerabilities due to functional convergence and functional promiscuity. Furthermore, for most known sea anemone toxins, the exact receptors they target are either unknown, or at best incomplete. In this review, we first provide an overview of the sea anemone venom system and then focus on the venom components. We have organised the venom components by distinguishing firstly between proteins and non-proteinaceous compounds, secondly between enzymes and other proteins without enzymatic activity, then according to the structural scaffold, and finally according to molecular target.

The CAP protein superfamily (Cysteine-rich secretory proteins (CRISPs), Antigen 5 (Ag5), and Pathogenesis-related 1 (PR-1) proteins) is widely distributed, but for toxinologists, snake venom CRISPs are the most familiar members. Although CRISPs are found in the majority of venoms, very few of these proteins have been functionally characterized, but those that have been exhibit diverse activities. Snake venom CRISPs (svCRISPs) inhibit ion channels and the growth of new blood vessels (angiogenesis). They also increase vascular permeability and promote inflammatory responses (leukocyte and neutrophil infiltration). Interestingly, CRISPs in lamprey buccal gland secretions also manifest some of these activities, suggesting an evolutionarily conserved function. As we strive to better understand the functions that CRISPs serve in venoms, it is worth considering the broad range of CRISP physiological activities throughout the animal kingdom. In this review, we summarize those activities, known crystal structures and sequence alignments, and we discuss predicted functional sites. CRISPs may not be lethal or major components of venoms, but given their almost ubiquitous occurrence in venoms and the accelerated evolution of svCRISP genes, these venom proteins are likely to have functions worth investigating.