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Background: Atheris spp. are small African vipers whose bites are rarely reported but can result in significant envenoming. There is no specific antivenom available. We describe a case of systemic A. chlorechis envenoming presenting with venom-induced consumption coagulopathy (VICC), snakebite-associated thrombotic microangiopathy (TMA), and local necrosis.

Case presentation: A 33-year-old man was bitten on the index finger by a captive A. chlorechis. Within 6 hours, early laboratory abnormalities progressed to VICC with markedly prolonged PT/aPTT, undetectable fibrinogen, elevated fibrin monomers, and factor V deficiency. Despite the administration of four vials of Inoserp™ Pan-Africa and repeated transfusions of fibrinogen and fresh frozen plasma, the patient continued to exhibit signs of coagulopathy for 48 hours. Thrombocytopenia, anaemia, schistocytes, and hyperbilirubinemia indicated snakebite-associated TMA, which resolved spontaneously without renal involvement. Progressive local necrosis developed on the finger and dorsal hand, ultimately requiring amputation of the proximal phalanx and surgical debridement.

Conclusion: This case demonstrates that A. chlorechis envenoming can produce both local and systemic toxicity. The absence of clinical improvement after Inoserp™ Pan-Africa is consistent with preclinical data showing limited cross-neutralization against Atheris venoms. Administration of clotting factors in the presence of unneutralised procoagulant toxins may have contributed to the development of TMA. Therefore, fresh frozen plasma and fibrinogen should be reserved for cases of coagulopathy with active bleeding or when an invasive procedure is being considered, particulary in the absence of a concomitant effective antivenom. The local necrosis highlights the potential for significant local sequelae, necessitating cautious but timely surgical intervention.

Snakebite envenoming remains a major public health issue in Brazil, with Bothrops genus responsible for most cases. To support public health planning, we analyzed epidemiological data from Paraná State and reported, for the first time, a species-level identification of snakes responsible for accidents in this region. The results revealed that Bothrops jararaca accounted for over 85% of cases, followed by Bothrops jararacussu, reinforcing their epidemiological and clinical relevance. Based on this evidence, two monoclonal antibodies were produced by hybridoma technology for application in a diagnostic tool for early identification of Bothrops spp. envenomation. The antibodies were sequenced and immunochemically characterized, and both specifically recognized bothropic metalloproteinases. When applied in a competitive ELISA, the assay detected venom concentrations as low as 60 ng/mL in sera spiked with B. jararaca and Bothrops alternatus and showed no reactivity with other medically relevant genera. Although detection of B. jararacussu, Bothrops moojeni and Bothrops neuwiedi required higher concentrations, these venoms remained detectable, indicating potential for broader application. Further optimization could enhance its sensitivity, enabling more effective detection across a wider spectrum of species. Together, these findings provide novel epidemiological and immunodiagnostic insights, that can guide the development of improved diagnostic platforms for Bothrops spp. envenoming.

Snake venoms represent a vast reservoir of bioactive molecules with both toxic and therapeutic potential. The Saharan horned viper (Cerastes cerastes), distributed across North Africa and the Middle East, produces a venom rich in proteins and peptides that modulate key physiological processes. This review synthesizes current knowledge on the pharmacological activities of Cerastes cerastes venom and its purified components, emphasizing their potential applications in medicine. Enzymes such as phospholipases A₂, serine proteinases, metalloproteinases, L-amino acid oxidases, and disintegrins have been isolated and characterized, displaying diverse biological effects. These include pro- and anticoagulant activities relevant to hemostasis, cytotoxic and anti-angiogenic properties with implications in cancer therapy, and antiparasitic effects against Leishmania and Schistosoma species. Furthermore, venom-derived LAAOs exhibit strong antibacterial activity, particularly against resistant pathogens such as MRSA, while emerging evidence highlights immunomodulatory and radioprotective roles. Despite their promise, challenges related to toxicity, stability, delivery, and potential immunogenicity must be addressed for successful clinical translation. Collectively, Cerastes cerastes venom exemplifies the therapeutic versatility of natural toxins and offers a valuable platform for the discovery and development of novel agents targeting cancer, infectious diseases, hemostatic disorders, and immune-mediated conditions.

Toosendanin (TSN) is the key bioactive component of Melia toosendan Sieb. et Zucc known for alleviating pain and expelling roundworms, but severe hepatotoxicity limited its further application. O-GlcNAcylation is a dynamic and reversible post-translational modification which has emerged as an important regulatory mechanism in cellular response to liver injury. In this study, we investigated the effect of aberrant O-GlcNAcylation and augmented O-GlcNAc signaling via Thiamet G (TMG) on TSN-induced ferroptosis in HepaRG cells. The O-GlcNAc transferase (OGT) expression and global O-GlcNAcylation level was significantly decreased accompanied by cell viability reduction and reactive oxygen species (ROS) production after the treatment with TSN. The western blotting and flow cytometry results showed that elevated O-GlcNAcylation by TMG treatment reversed the adverse changes induced by TSN in ferroptosis-related markers, including lipid ROS accumulation, glutathione depletion, and glutathione peroxidase 4 (GPX4) degradation. Additionally, immunoprecipitation demonstrated that TMG reversed TSN-induced nuclear factor erythroid 2-related factor 2 (Nrf2) O-GlcNAcylation inhibition and its ubiquitination enhancement in HepaRG cells. Furthermore, screening with the UbiBrowser database and mass spectrometry identified ubiquitin-specific protease 7 (USP7) as the potential deubiquitinating enzyme that mediates TMG-induced Nrf2 stabilization. In conclusion, TSN decreased global O-GlcNAcylation levels and increased the susceptibility of HepaRG cells to ferroptosis-associated hepatotoxicity by suppressing the Nrf2/GPX4 pathway.

Proteomic characterization of snake venoms is essential for understanding the molecular basis of their evolution and for identifying bioactive compounds of therapeutic interest. The Montivipera species endemic to the Near and Middle East region remain poorly studied despite their interesting biological activities. Previous analyses of Montivipera venoms have provided only partial proteomic profiles, with notable discrepancies between studies. To address this gap, we conducted a proteomic analysis of five Montivipera species, including M. bornmuelleri, M. bulgardaghica, M. albizona, M. raddei and M. xanthina. We also analyzed the venom of Macrovipera lebetina ssp. to provide a broader comparative framework. These venoms were investigated using an integrated approach combining SDS-PAGE, RP-HPLC and shotgun proteomics, using both trypsin and multi-enzymatic limited digestions to maximize protein identification and coverage. SDS-PAGE and RP-HPLC analyses revealed the remarkable complexity and diversity of Montivipera venoms, which were further confirmed by shotgun proteomics, identifying between 129 and 179 proteins and peptides per species. The major protein families detected included snake venom metalloproteinases, phospholipases A₂, venom serine proteases, C-type lectins, venom vascular-endothelial growth factors, and disintegrins. Notably, the relative abundance of these protein families varied across species, suggesting interspecific differences in envenomation profiles. Comparative analysis revealed a high degree of similarity among Montivipera species, with 39 shared proteins across all five venoms. Our findings confirmed the major toxin families previously reported in Montivipera venoms and revealed the presence of several low-abundance protein families that were not previously identified. Thus, this study highlights both the conserved and unique features of Montivipera venom proteomes, offering a valuable foundation for future functional and evolutionary investigations.

Sea anemones are a rich source of venom peptides, many of which target voltage-gated sodium channels (Nav), having immense potential for therapeutic development. In this study, we employed a transcriptomics-guided approach to predict and functionally characterize a Nav-targeting peptide from the sea anemone Bunodosoma goanense. A single putative peptide transcript with homology to known sodium channel modulators was discovered. This transcript-derived peptide was chemically synthesized and tested for activity. Electrophysiological assays employing two-electrode voltage clamp (TEVC) on Xenopus laevis oocytes overexpressing Nav1.4 and Nav1.5 channels, along with contraction paralysis assay, confirmed its functional activity. Subsequent tentacle venom purification isolated a native peptide with the same bioactivity. Our work demonstrates the power of predictive transcriptomics for sustainable venom peptide discovery.