Ananteris is a scorpion genus that inhabits dry and seasonal areas of South and Central America. It is located in a distinctive morpho-group of Buthids, the \'Ananteris group\', which also includes species distributed in the Old World. Because of the lack of information on venom composition, the study of Ananteris species could have biological and medical relevance. We conducted a venomics analysis of Ananteris platnicki, a tiny scorpion that inhabits Panama and Costa Rica, which shows the presence of putative toxins targeting ion channels, as well as proteins with similarity to hyaluronidases, proteinases, phospholipases A2, members of the CAP-domain family, and hemocyanins, among others. Venom proteolytic and hyaluronidase activities were corroborated. The determination of the primary sequences carried out by mass spectrometry evidences that several peptides are similar to the toxins present in venoms from Old World scorpion genera such as Mesobuthus, Lychas, and Isometrus, but others present in Tityus and Centruroides toxins. Even when this venom displays the characteristic protein families found in all Buthids, with a predominance of putative Na+-channel toxins and proteinases, some identified partial sequences are not common in venoms of the New World species, suggesting its differentiation into a distinctive group separated from other Buthids.

In sensory neurons that transmit pain signals, whether acute or chronic, voltage-gated sodium channels (VGSCs) are crucial for regulating excitability. NaV1.1, NaV1.3, NaV1.6, NaV1.7, NaV1.8, and NaV1.9 have been demonstrated and defined their functional roles in pain signaling based on their biophysical properties and distinct patterns of expression in each subtype of sensory neurons. Scorpions and spiders are traditional Chinese medicinal materials, belonging to the arachnid class. Most of the studied species of them have evolved venom peptides that exhibit a wide variety of knottins specifically targeting VGSCs with subtype selectivity and conformational specificity. This review provides an overview on the exquisite knottins from scorpion and spider venoms targeting pain-related NaV channels, describing the sequences and the structural features as well as molecular determinants that influence their selectivity on special subtype and at particular conformation, with an aim for the development of novel research tools on NaV channels and analgesics with minimal adverse effects.

BACKGROUND: Species of the Jatropha genus (Euphorbiaceae) are used indiscriminately in traditional medicine to treat accidents involving venomous animals. Jatropha mutabilis Baill., popularly known as \"pinhão-de-seda,\" is found in the semi-arid region of Northeastern Brazil. It is widely used as a vermifuge, depurative, laxative, and antivenom.
OBJECTIVE: Obtaining the phytochemical profile of the latex of Jatropha mutabilis (JmLa) and evaluate its acute oral toxicity and inhibitory effects against the venom of the scorpion Tityus stigmurus (TstiV).
METHODS: The latex of J. mutabilis (JmLa) was obtained through in situ incisions in the stem and characterized using HPLC-ESI-QToF-MS. Acute oral toxicity was investigated in mice. The protein profile of T. stigmurus venom was obtained by electrophoresis. The ability of latex to interact with venom components (TstiV) was assessed using SDS-PAGE, UV-Vis scanning spectrum, and the neutralization of fibrinogenolytic and hyaluronidase activities. Additionally, the latex was evaluated in vivo for its ability to inhibit local edematogenic and nociceptive effects induced by the venom.
RESULTS: The phytochemical profile of the latex revealed the presence of 75 compounds, including cyclic peptides, glycosides, phenolic compounds, alkaloids, coumarins, and terpenoids, among others. No signs of acute toxicity were observed at a dose of 2000 mg/kg (p.o.). The latex interacted with the protein profile of TstiV, inhibiting the venom\'s fibrinogenolytic and hyaluronidase activities by 100%. Additionally, the latex was able to mitigate local envenomation effects, reducing nociception by up to 56.5% and edema by up to 50% compared to the negative control group.
CONCLUSIONS: The latex of Jatropha mutabilis exhibits a diverse phytochemical composition, containing numerous classes of metabolites. It does not present acute toxic effects in mice and has the ability to inhibit the enzymatic effects of Tityus stigmurus venom in vitro. Additionally, it reduces nociception and edema in vivo. These findings corroborate popular reports regarding the antivenom activity of this plant and indicate that the latex has potential for treating scorpionism.

Accidents caused by venomous animals, especially scorpions, are a major public health problem due to the increase in incidence in recent decades, since scorpion species have become well adapted to urbanized environments. Nonetheless, the impact of urbanization in scorpionism is not clear. The objective of this study is to correlate the variation in the incidence of scorpion accidents with the rate of urbanized area. This was a retrospective, epidemiological study of accidents by scorpions in 376 of the most populous Brazilian cities in 2019 and compared to ten years earlier, using Spearman\'s correlation coefficient. Data were obtained by accessing DATASUS/TABNET and IBGE Cidades platforms. A weak negative correlation between scorpion stings and urbanization was found in 2009 (rs = -0.145). The correlation between the variation in the incidence of scorpionism and the percentage of urbanized area was not significant. Although the highest incidence of scorpionism occurs in-more urbanized environments, there is a wide distribution of scorpion accidents, especially in tropical and subtropical regions due to climatic conditions, the level of urbanization of Brazilian municipalities was not the major factor in the increase of scorpion accidents.

Alternative recombinant sources of antivenoms have been successfully generated. The application of such strategies requires the characterization of the venoms for the development of specific neutralizing molecules against the toxic components. Five toxic peptides to mammals from the Mexican scorpion Centruroides villegasi were isolated by chromatographic procedures by means of gel filtration on Sephadex G-50, followed by ion-exchange columns on carboxy-methyl-cellulose (CMC) resins and finally purified by high-performance chromatography (HPLC) columns. Their primary structures were determined by Edman degradation. They contain 66 amino acids and are maintained well packed by four disulfide bridges, with molecular mass from 7511.3 to 7750.1 Da. They are all relatively toxic and deadly to mice and show high sequence identity with known peptides that are specific modifiers of the gating mechanisms of Na+ ion channels of type beta-toxin (β-ScTx). They were named Cv1 to Cv5 and used to test their recognition by single-chain variable fragments (scFv) of antibodies, using surface plasmon resonance. Three different scFvs generated in our laboratory (10FG2, HV, LR) were tested for recognizing the various new peptides described here, paving the way for the development of a novel type of scorpion antivenom.

UNASSIGNED: The expansion of the territory of human habitation leads to inevitable interference in the natural range of distribution of one or another species of animals, some of which may be dangerous for human life. Scorpions-the Arachnida class and order Scorpiones-can be considered as such typical representatives. Scorpions of the Buthidae family pose a particular danger to humans. However, LD50 has not yet been defined for many species of this family, in particular, new representatives of the genus Leiurus. Leiurus macroctenus is a newly described species of scorpion distributed in Oman, and the toxicity of its venom is still unknown. Estimating the LD50 of the venom is the first and most important step in creating the antivenom and understanding the medical significance of the researched animal species. The purpose of this study was to determine the lethal dose (LD100), the maximum tolerated dose (LD0), and the average lethal dose (LD50) in rats when using Leiurus macroctenus scorpion venom.
UNASSIGNED: 15 sexually mature scorpions were used in the study, which were kept in the same conditions and milked by a common method (electric milking). For the study, 60 male rats were used, which were injected intramuscularly with 0.5 ml of venom solution with a gradual increase in the dose (5 groups, 10 rats in each), and 10 rats were injected intramuscularly with physiological solution as control group. LD calculations were done using probit analysis method in the modification of the method by V.B. Prozorovsky. The LD0 of Leiurus macroctenus scorpion venom under the conditions of intramuscular injection was 0.02 mg/kg, LD100 was 0.13 mg/kg, and LD50 was 0.08 ± 0.01 mg/kg.
UNASSIGNED: The analysis of scientific publications and other sources of information gives reason to believe that Leiurus macroctenus has one of the highest values of LD50 not only among scorpions but also among all arthropods in the world. All these point to the significant clinical importance of this species of scorpion and require further research that will concern the toxic effect of its venom on various organ systems. Determining the LD50 of the venom for new scorpion species is crucial for creating effective antivenoms and understanding the medical implications of envenomation by this species.

Scorpion sting is a medical burden globally but especially frequent hotspots of scorpion biodiversity. In Iran, one of those hotspot countries, many fatalities occur in the South as well as the Southwest and are thought to be caused by Hemiscorpius lepturus. Accordingly, those are used for antivenom production. However, recent surveys revealed that indeed a different species Hemiscorpius acanthocercus is responsible for most accidents in the South, while H. lepturus is primarily causing the fatalities in the Southwest and thus Iranian scorpion antivenom needs to be refined in that respect. Such a refined antivenom would need to cover both species of Hemiscorpius. In response, the Iranian Ministry of Health requested the adjustment of the production line from local antivenom suppliers but until today no action has been taken.

In this study, we report the innovative application of whole-cell patch-clamp electrophysiology in assessing broad-spectrum neutralisation by three different antivenoms, of venoms from the medically significant scorpion genus Centruroides. Envenomations by as many as 21 species from the Centruroides genus result in up to 300,000 envenomations per year in Mexico, which poses significant and potentially life-threatening pathophysiology. We first evaluated the in vitro manifestation of envenomation against two human voltage-gated sodium (hNaV) channel subtypes: hNaV1.4 and hNaV1.5, which are primarily expressed in skeletal muscles and cardiomyocytes, respectively. The neutralisation of venom activity was then characterised for three different antivenoms using a direct competition model against the more potent target, hNaV1.4. While broad-spectrum neutralisation was identified, variation in neutralisation arose for Centruroides elegans, C. limpidus, C. noxius and C. suffusus venoms, despite the presence of a number of these venoms within the immunising mixture. This raises questions regarding the truly \"broad\" neutralisation capacity of the antivenoms. This study not only extends previous validation of the in vitro investigation of antivenom efficacy utilising the whole-cell patch-clamp technique but also underscores the potential of this animal-free model in exploring cross-reactivity, experimental scalability, and most importantly, informing clinical management practices regarding the administration of antivenom in Mexico.

Thermally stable full-length scorpion toxin peptides and partially degraded peptides with complete disulfide bond pairing are valuable natural peptide resources in traditional Chinese scorpion medicinal material. However, their pharmacological activities are largely unknown. This study discovered BmKcug1a-P1, a novel N-terminal degraded peptide, in this medicinal material. BmKcug1a-P1 inhibited hKv1.2 and hKv1.3 potassium channels with IC50 values of 2.12 ± 0.27 μM and 1.54 ± 0.28 μM, respectively. To investigate the influence of N-terminal amino acid loss on the potassium channel inhibiting activities, three analogs (i.e., full-length BmKcug1a, BmKcug1a-P1-D2 and BmKcug1a-P1-D4) of BmKcug1a-P1 were prepared, and their potassium channel inhibiting activities on hKv1.3 channel were verified by whole-cell patch clamp technique. Interestingly, the potassium channel inhibiting activity of full-length BmKcug1a on the hKv1.3 channel was significantly improved compared to its N-terminal degraded form (BmKcug1a-P1), while the activities of two truncated analogs (i.e., BmKcug1a-P1-D2 and BmKcug1a-P1-D4) were similar to that of BmKcug1a-P1. Extensive alanine-scanning experiments identified the bonding interface (including two key functional residues, Asn30 and Arg34) of BmKcug1a-P1. Structural and functional dissection further elucidated whether N-terminal residues of the peptide are located at the bonding interface is important in determining whether the N-terminus significantly influences the potassium channel inhibiting activity of the peptide. Altogether, this research identified a novel N-terminal degraded active peptide, BmKcug1a-P1, from traditional Chinese scorpion medicinal material and elucidated how the N-terminus of peptides influences their potassium channel inhibiting activity, contributing to the functional identification and molecular truncation optimization of full-length and degraded peptides from traditional Chinese scorpion medicinal material Buthus martensii Karsch.

Scorpion venoms have proven to be excellent sources of antimicrobial agents. However, although many of them have been functionally characterized, they remain underutilized as pharmacological agents, despite their evident therapeutic potential. In this review, we discuss the physicochemical properties of short scorpion venom antimicrobial peptides (ssAMPs). Being generally short (13-25 aa) and amidated, their proven antimicrobial activity is generally explained by parameters such as their net charge, the hydrophobic moment, or the degree of helicity. However, for a complete understanding of their biological activities, also considering the properties of the target membranes is of great relevance. Here, with an extensive analysis of the physicochemical, structural, and thermodynamic parameters associated with these biomolecules, we propose a theoretical framework for the rational design of new antimicrobial drugs. Through a comparison of these physicochemical properties with the bioactivity of ssAMPs in pathogenic bacteria such as Staphylococcus aureus or Acinetobacter baumannii, it is evident that in addition to the net charge, the hydrophobic moment, electrostatic energy, or intrinsic flexibility are determining parameters to understand their performance. Although the correlation between these parameters is very complex, the consensus of our analysis suggests that there is a delicate balance between them and that modifying one affects the rest. Understanding the contribution of lipid composition to their bioactivities is also underestimated, which suggests that for each peptide, there is a physiological context to consider for the rational design of new drugs.