A study of the venom proteome of the buthid Hottentotta judaicus

 

Adolfo Borges and co-workers recently published a study of the venom proteome of Hottentotta judaicus (Simon, 1872) (Buthidae). The study identified 55 components across 15 protein families, with ion channel toxins and enzymes predominating. 

This stuff is not within my scorpion competence, but I understand that the results are expanding the  repertoire of potential bioactive components prompts in the venom and that H. judaicus venom may pose a larger risk to human than previously assumed, especially for children or those with underlying cardiovascular conditions.

Abstract:
The scorpion Hottentotta judaicus inhabits the Levant region of the Middle East, including Lebanon, Jordan, Palestine, and Israel. While previous research focused on its insecticidal properties and sodium-channel-targeting toxins, its venom remains largely unexplored using modern proteomic approaches. We analyzed the venom composition of H. judaicus from Lebanese specimens using nESI-MS/MS, MALDI-TOF MS, SDS-PAGE, and RP-HPLC. Venom lethality in mice was assessed (LD₅₀ = 11.87 [6.59–17.16] mg/kg, i.p.), confirming moderate toxicity to vertebrates. RP-HPLC on C18 resolved 37 peaks, with 25 eluting between 20–40% acetonitrile. Reducing SDS-PAGE revealed predominant components < 10 kDa and minor bands at 31, 46, and 77 kDa. MaLDI-TOF MS detected 20 components from 1,000–12,000 m/z. A bottom-up shotgun nLC-MS/MS approach, following in-gel tryptic digestion of venom, identified 55 components across 15 protein families. Ion channel-active toxins [K⁺ (7), Na⁺ (16), Cl⁻ (1), ryanodine receptor (1)] and enzyme components (17) were predominant. This study provides proteomic evidence of H. judaicus venom components previously only identified at the transcriptomic level and reveals a richer venom profile than anticipated. Novel identified components include alternative β-subunits of lipolysis-activating proteins, as well as homologs of Olivierus martensii antimicrobial peptide inhibitor HAP- 1, Leiurus hebraeus Lqhβ1, Parabuthus transvaalicus Birtoxin, and peptide Hj2a from Hottentotta jayakari exhibiting dual α/β-toxin activity on Nav1.1 channels. This expanding repertoire of potential bioactive components prompts a reevaluation of the pathophysiological consequences of H. judaicus envenomation in humans and further exploration of their potential biomedical applications.

Reference:
Borges A, Lomonte B, de Arias AR, Fernandez J. Proteomic characterization and lethality of the venom of the Black Judean scorpion, Hottentotta judaicus (Buthidae): expanded toxin diversity and revisited toxicological significance. Arch Toxicol. 2025. Published online 10. September 2025. [Subscription required for full text]

Thanks to Adolfo for informing me about their article!

A biochemical and proteomic study of Amazonian scorpion venoms

 

Studying the venom composition of scorpions is important. It is important to know the venom composition in medical important species to understand their pathological effect and better be able to develop antivenom or treatment. In addition, scorpion venom is a treasure chest filled with different peptides and toxins that can be used to develop medicines. 

Karla Bordon and co-workers recently published a study presenting a comprehensive biochemical characterization of venom from three Amazonian species, Tityus metuendus Pocock, 1897, T. silvestris Pocock, 1897 (both Buthidae) and Brotheas amazonicus  Lourenço, 1988 (Chactidae).

According to the article, "the results suggest a correlation between ecological divergence and venom composition, with implications for both toxicity and antivenom development".

Abstract:
Scorpionism is a growing public health concern in Brazil, with the Amazon region presenting the highest mortality rates but remaining understudied, especially regarding local scorpion venoms composition. This study presents the first comprehensive biochemical characterization of venoms from three Amazonian species—Tityus metuendus (TmetuV), Tityus silvestris (TsilvV), and Brotheas amazonicus (BamazV)—using an integrated approach combining Multi-Enzymatic Limited Digestion (MELD)-based bottom-up proteomics, highresolution LC-MS/MS, chromatography, zymography, and enzymatic assays. Tityus serrulatus venom was included as a reference. Significant biochemical differences were observed: TsilvV was rich in 20–30 kDa proteins and showed strong metalloprotease activity; BamazV exhibited high molecular weight proteins and potent phospholipase A2 (PLA2)
activity but lacked proteolytic and fibrinogenolytic activities; TmetuV showed the highest hyaluronidase activity and abundance of α-KTx neurotoxins. Zymography revealed a conserved ~45 kDa hyaluronidase in all species. Three novel components were partially characterized: BamazPLA2 (Group III PLA2), Tmetu1 (37-residue α-KTx), and TsilvMP_A (a metalloprotease homologous to antarease). This is the first application of MELD-based proteomics to Amazonian scorpion venoms, revealing molecular diversity and functional divergence within Tityus and Brotheas, emphasizing the need for region-specific antivenoms. These findings provide a foundation for future pharmacological studies and the discovery of bioactive peptides with therapeutic potential.

Reference:
Bordon KC, Santos GC, Martins JG, Wiezel GA, Amorim FG, Crasset T, et al. Pioneering Comparative Proteomic and Enzymatic Profiling of Amazonian Scorpion Venoms Enables the Isolation of Their First α-Ktx, Metalloprotease, and Phospholipase A2. Toxins. 2025;17(8):411. [Open Access]

Thanks to Jonas Martins for sending me their article!

A major and important review on scorpionism, toxicology, medical important species and their distribution in Amazonia

 

Amazonia hosts a large numbers of scorpions, many of which are of medical importance in humans. All of these belong to the species rich genus Tityus C. L. Koch, 1836 (Buthidae). There have been a lot of research on scorpionism in South America and Tityus in particular, but few reviews looking on the larger picture.

Adolfo Borges and co-workers have now published a major review going through the literature on scorpionism in Amazonia, but also mapping all Tityus species in the region and their medical importance. Updated knowledge on taxonomy and phylogeny of the Tityus populations is essential in the context of public health and preventing accidents involving dangerous scorpions. The article also sum up the knowledge on venom toxicology and physiopathology of the species in the region.

This is an important article that sums up much of the currently known information on scorpionism in Amazonia, species involved and their distribution.

Abstract:
Venom from Amazonian scorpions of the genus Tityus contains components capable of eliciting a distinct clinical, mostly neurological, syndrome. This contrasts with the mainly autonomic manifestations produced after envenomation by congeneric southern and northern South American species. Herein, we summarize Pan-Amazonian scorpionism by synthesizing available toxinological, clinical, and molecular data gathered from all affected areas in Amazonia, including Brazil, Ecuador, Colombia, Peru, Venezuela, and French Guiana. We searched multiple databases, as well as our own records, for reports of scorpion envenomations in Amazonia by confirmed Tityus spp., and compared the clinical manifestations. To help uncover clinical and venom relationships among problematic species, we explored phylogenetic relationships with a rate-calibrated analysis of mitochondrial COI data from available species. The possible existence of diversity gradients for venom toxic and immunogenic components despite the predicted strong phylogenetic association among species is underscored by discussed clinical and toxinological findings. A multicentric effort, involving all nations affected by this neglected disease, is urgently needed to offer alternatives for treating and understanding this pathology, including the preparation of neutralizing antibodies with a broad range of efficacy.

Reference:
Borges A, Graham MR, Cândido DM, Pardal PPO. Amazonian scorpions and scorpionism: integrating toxinological, clinical, and phylogenetic data to combat a human health crisis in the world’s most diverse rainfores. J Venom Anim Toxins Incl Trop Dis. 2021;27:Published online: 29 November 2021. [Open Access]

Thanks to Adolfo Borges and Victor Fet for sending me this article!

Scorpion venom can kill dangerous, resistant bacterias in a safe way

I usually do not post much about biochemical and toxicology research on scorpion venom as I have very little expertise on these topics. As many of you probably have noticed, there is a lot of research on scorpion venom trying to identify components in the venom that can be used for medical and/or commercial purposes. Because of this, scorpion venom is now considered one of the most expensive materials on earth. This week a very interesting study was published.

Edson Norberto Carcamo-Noriegaa and co-workers have identified twopreviously unknown benzoquinones in the venom of the Mexican scorpion Diplocentrus melici Armas, Martin-Frias & Berea, 2004 (Scorpionidae). The study shows that these two compounds can kill dangerous staphylococcus and tuberculosis bacteria in a safe way. The researchers also were able to synthesize the two compounds, making this a very promising tool for a future medicine against dangerous and resistant bacterias.

If you can not access the article, you can check out this news report from Stanford University summing up the main findings.

Abstract:
Two 1,4-benzoquinone derivatives, found in the venom of the scorpion Diplocentrus melici following exposure to air, have been isolated, characterized, synthesized, and assessed for antimicrobial activities. Initially a white, viscous liquid, the extracted venom colors within minutes under ambient conditions. From this colored mixture, two compounds, one red, the other blue, were isolated and purified using chromatography. After a variety of NMR and mass spectrometry experiments, the red compound was determined to be 3,5- dimethoxy-2-(methylthio)cyclohexa-2,5-diene-1,4-dione, and the blue compound was determined to be 5-methoxy-2,3- bis(methylthio) cyclohexa-2,5-diene-1,4-dione. Because extremely small amounts of these compounds were isolated from the scorpion venom, we developed laboratory syntheses from commercially available precursors, allowing us to produce sufficient quantities for crystallization nd biological assays. The red benzoquinone is effective against Staphylococcus aureus [minimum inhibitory concentration (MIC) = 4 μg/mL], while the blue benzoquinone is active against Mycobacterium tuberculosis (MIC = 4 μg/mL) and even against a multidrug-resistant (MDR) strain with nearly equal effectiveness. The bactericidal effects of both benzoquinones show comparable activity to commercially available antibiotics used against these pathogens and were cytotoxic to neoplastic cell lines, suggesting
their potential as lead compounds for the development of novel antimicrobial and anticancer drugs. Importantly, the blue benzoquinone was also effective in vivo with mouse models of MDR tuberculosis infection. After treatment for 2 mo, four mice with late-stage active MDR tuberculosis had a significant decrease in pulmonary bacillary loads and tissue damage. Healthy mice served as negative controls and tolerated treatment well, without adverse side effects.

Reference:
Carcamo-Noriega EN, Sathyamoorthi S, Banerjee S, Gnanamani E, Mendoza-Trujillo M, Mata-Espinosa D, et al. 1,4-Benzoquinone antimicrobial agents against Staphylococcus aureus and Mycobacterium tuberculosis derived from scorpion venom. Proceedings of the National Academy of Sciences. 2019:201812334. [Subscription required for full text]

Thanks to Matt Simon for informing me about this interesting article!

The acid in the venom makes a scorpion's sting extra painful

Fortunately, most scorpions are harmless to humans. But getting stung usually hurt, and for many buthids it hurts a lot. It is known that special toxins (peptids) in the venom cocktail are responsible for the pain, but a new study by Shilong Yang, and co-workers shows that the acid in the venom increase the pain effects of the toxins significantly and thereby maximizing the toxin potency.

If you want to learn more about this study, check out this blog report from Phys Org that explains the mechanism more in detail.

Abstract:
Venomous animals use peptide toxins for hunting and self-defense. To achieve these goals, toxins need to bind to their targets with high affinity due to the small amount that a single bite or sting can deliver. The scorpion toxin BmP01 is linked to sting-induced excruciating pain; however, the reported minimum concentrations for activating TRPV1 channel or inhibiting voltage-gated potassium (Kv) channels (both in the micromolar range) appear too high to be biologically relevant. We show that the effective concentration of BmP01 is highly pH-dependent—it increases by about 10-fold in inhibiting Kv channels upon a 1-U drop in pH but decreases more than 100-fold in activating TRPV1. Mechanistic investigation revealed that BmP01 binds to one of the two proton-binding sites on TRPV1 and, together with a proton, uses a one-two punch approach to strongly activate the nociceptive channel. Because most animal venoms are acidic, proton-facilitated synergistic actionmay represent a general strategy for maximizing toxin potency.

Reference:
Yang S, Yang F, Zhang B, Lee BH, Li B, Luo L, et al. A bimodal activation mechanism underlies scorpion toxin–induced pain. Science Advances. 2017;3(8). [Open Access]