Search Results (82)

Background/Objectives: Most snakebite incidents in Latin America are caused by species of the Bothrops genus. Their venom induces severe local effects, against which antivenom therapy has limited efficacy. Metabolites derived from Coffea arabica have demonstrated anti-inflammatory and anticoagulant properties, suggesting their potential as therapeutic agents to inhibit the local effects induced by B. asper venom. Methods: Three enzymatic assays were performed: inhibition of the procoagulant and amidolytic activities of snake venom serine proteinases (SVSPs); inhibition of the proteolytic activity of snake venom metalloproteinases (SVMPs); and inhibition of the catalytic activity of snake venom phospholipases A₂ (PLA_2s). Additionally, molecular docking studies were conducted to propose potential inhibitory mechanisms of the metabolites chlorogenic acid, caffeine, and caffeic acid. Results: Green and roasted coffee extracts partially inhibited the enzymatic activity of SVSPs and SVMPs. Notably, the green coffee extract, at a 1:20 ratio, effectively inhibited PLA₂ activity. Among the individual metabolites tested, partial inhibition of SVSP and PLA₂ activities was observed, whereas no significant inhibition of SVMP proteolytic activity was detected. Chlorogenic acid was the most effective metabolite, significantly prolonging plasma coagulation time and achieving up to 82% inhibition at a concentration of 62.5 μM. Molecular docking analysis revealed interactions between chlorogenic acid and key active site residues of SVSP and PLA₂ enzymes from B. asper venom. Conclusions: The roasted coffee extract demonstrated the highest inhibitory effect on venom toxins, potentially due to the formation of bioactive compounds during the Maillard reaction. Molecular modeling suggests that the tested inhibitors may bind to and occupy the substrate-binding clefts of the target enzymes. These findings support further in vivo research to explore the use of plant-derived polyphenols as adjuvant therapies in the treatment of snakebite envenoming. Full article

Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The puff adder (Bitis arietans) and saw-scaled viper (Echis romani) have cytotoxic venoms that cause permanent injury via dermonecrosis around the bite site. Identifying the cytotoxic toxins within these venoms will allow for the development of targeted treatments to prevent snakebite morbidity. In this study, venoms from both species were fractionated using gel filtration chromatography, and a combination of cytotoxicity approaches, SDS-PAGE gel electrophoresis, and enzymatic assays were applied to identify the venom cytotoxins in the resulting fractions. Our results indicate that snake venom metalloproteinase (SVMP) toxins are responsible for causing cytotoxic effects across both venoms. The PI subclass of SVMPs is likely the main driver of cytotoxicity following envenoming by B. arietans, while the structurally distinct PIII subclass of SVMPs is mostly responsible for conveying this effect in E. romani venom. Identifying distinct SVMPs as cytotoxicity-causing toxins in these two African viper venoms will facilitate the future design and development of novel therapeutics targeting these medically important venoms, which in turn could help to mitigate the severe life- and limb-threatening consequences of tropical snakebites. Full article

Snakebite is a significant global public health challenge, and the limited application of antivenom has driven the exploration of novel therapies. Combination therapy using small-molecule drugs targeting phospholipases A₂ (PLA2) and metalloproteinases (SVMP) in venom shows great potential. Although Rhamnetin and RXP03 exhibit notable anti-phospholipase and anti-metalloproteinase activities, respectively, their antiophidic potential remains poorly explored. This study aims to evaluate the inhibitory effects of Rhamnetin and RXP03 on snake venom toxicity. Methodologically, we conducted in vitro enzymatic assays to quantify PLA₂/SVMP inhibition, murine models of envenomation (subcutaneous/intramuscular venom injection) to assess local tissue damage and systemic toxicity, and histopathological/biochemical analyses. In vitro experiments demonstrated that Rhamnetin effectively inhibited PLA₂ activity while RXP03 showed potent suppression of SVMP activity, with their combination significantly reducing venom-induced hemorrhagic activity. In murine models, the combined therapy markedly alleviated venom-triggered muscle toxicity and ameliorated oxidative stress. Furthermore, the combination enhanced motor performance and survival rate in mice, improved serum biochemical parameters, corrected coagulation disorders, and attenuated pathological damage in liver, kidney, heart, and lung tissues. This research demonstrates that dual-targeted therapy against metalloproteinases and phospholipases in snake venom can effectively prevent a series of injuries caused by snake venom. Collectively, the combined application of Rhamnetin and RXP03 exhibits significant inhibitory effects on a variety of venom-induced toxicities, providing pharmacological evidence for the development of antivenom therapies. However, the efficacy validation in this study was limited to murine models, and there is a discrepancy with clinical needs for delayed treatment in real-world envenomation scenarios. Despite these limitations, the findings provide robust preclinical evidence supporting the Rhamnetin–RXP03 combination therapy as a cost-effective, broad-spectrum antivenom strategy. Future studies are required to optimize dosing regimens and evaluate clinical translatability. Full article

Snake venoms contain numerous toxic proteins, but low-abundance proteins often remain uncharacterized due to identification challenges. This study employs a bioinformatics approach to identify and structurally model low-abundance proteins from the venom gland transcriptomes of Bothrops asper and Bothrops jararaca. Using tools such as tblastn, Jalview, and CHIMERA, we analyzed sequences and structural features of proteins including arylsulfatase, CRISP (Cysteine-Rich Secretory Protein), von Willebrand factor type D (vWFD), and dihydroorotate dehydrogenase (DHODH), and identified potential new isoforms of SVMP-PIIIb (Ba_1) and botrocetin in B. asper. Protein models were generated with AlphaFold2, compared with crystallized structures from the Protein Data Bank (PDB), and validated using Procheck, ERRAT, and Verify3D. Conserved motifs and domains were annotated through Pfam and InterPro, revealing structural elements that suggest possible roles in venom physiology and toxicity. These findings emphasize the potential of computational biology to characterize structurally relevant but experimentally inaccessible venom proteins, and to lay the groundwork for future functional validation. Full article

Toxoplasmosis is an alarming public health problem that affects more than one-third of the world’s population. In our work, we investigated the antiparasitic effects of catalytically active [BpMP-I and Jararhagin (Jar)] and catalytically inactive [Jararhagin-C (Jar-C)] snake venom metalloproteinases (SVMPs) in human HeLa cells. These toxins impaired the parasite invasion and intracellular growth, and modulated IL-6, IL-8, and MIF cytokines that control the cell susceptibility and response against T. gondii. Furthermore, we verified that the antiprotozoal activities are not restricted to the presence of the proteolytic domain, and the adhesive domains participate in the control of T. gondii infection. Also, by analyzing the structures of Jar and Jar-C through molecular modeling and dynamics, we observed that the adhesive domains in Jar-C are more exposed due to the absence of the proteolytic domain, which could favor the interaction with different targets. Our investigation on the role of SVMP domains in combating T. gondii infection highlights their potential application as biotechnological tools for creating more effective treatments for toxoplasmosis. Full article

Chinese coral snakes (Sinomicrurus) are highly neglected regarding their venom profiles and harm to humans, which impedes our ability to deeply understand their biological properties and explore their medicinal potential. In this study, we performed a comparative analysis to reveal the venom profiles of two Chinese coral snakes in terms of their venom yields, proteomic profiles, and immunorecognition by commercial antivenoms. The results showed that Sinomicrurus kelloggi expels more venom (lyophilized venom mass) than Sinomicrurus maccelellandi but possesses a similar solid venom content. These interspecific differences in venom yield were influenced by the snout–vent length. The venoms of these two species varied in their electrophoretic profiles, as well as in the presence or absence and relative abundance of protein families. They exhibited a 3-FTx-predominant phenotype, where the S. maccelellandi venom was dominated by 3-FTx (32.43%), SVMP (23.63%), PLA₂ (19.88%), and SVSP (12.61%), while the S. kelloggi venom was dominated by 3-FTx (65.81%), LAAO (11.35%), and AMP (10.09%). While both the commercial Naja atra and Bungarus multicinctus antivenoms could immunorecognize these two Chinese coral snake venoms, the N. atra antivenom possessed a higher neutralization capability than the B. multicinctus antivenom for both species of coral snakes. Our findings show significant interspecific variations in the venom profiles of these Sinomicrurus snakes for the first time. We suggest screening or preparing specific antivenoms with high efficiency for the clinical treatment of envenomation caused by these snakes. Full article

Previous proteomic studies of viperid venom revealed that it is mainly composed of metalloproteinases (SVMPs), serine proteinases (SVSPs), phospholipase A2 (PLA2), and C-type lectins (CTLs). However, other proteins appear in minor amounts that affect prey and need to be identified. This study aimed to identify novel toxic proteins in the venom gland transcriptome of Bothrops asper and Bothrops jararaca, using data from NCBI. Bioinformatics tools were used to assemble, identify, and compare potentially novel proteins in both species, and we performed functional annotation with BLASTX against the NR database. While previous assemblies have been performed for B. jararaca, this is the first assembly of the B. asper venom gland transcriptome. Proteins with potentially novel functions were identified, including arylsulfatase and dihydroorotate dehydrogenase, among others, that could have implications for venom toxicity. These results suggest that the identified proteins may contribute to venom toxic variation and provide new opportunities for antivenom research. The study improves the understanding of the protein composition of Bothrops venom and suggests new possibilities for the development of treatments and antivenoms. Full article

Kraits are venomous snakes of the genus Bungarus from the family Elapidae. Their venom typically demonstrates neurotoxicity; however, the toxicity is significantly influenced by the snake’s species and geographical origin. Among the Bungarus species, Bungarus suzhenae and B. bungaroides have been poorly studied, with little to no information available regarding their venom composition. In this study, a proteomic approach was employed using LC-MS/MS to identify proteins from trypsin-digested peptides. The analysis revealed 102 venom-related proteins from 18 distinct functional protein families in the venom of B. suzhenae, with the primary components being three-finger toxins (3-FTx, 25.84%), phospholipase A₂ (PLA₂, 40.29%), L-amino acid oxidase (LAAO, 10.33%), Kunitz-type serine protease inhibitors (KUN, 9.48%), and snake venom metalloproteinases (SVMPs, 6.13%). In the venom of B. bungaroides, 99 proteins from 17 families were identified, with primary components being 3-FTx (33.87%), PLA₂ (37.91%), LAAO (4.21%), and KUN (16.60%). Enzymatic activity assays confirmed the presence of key venom enzymes. Additionally, the LD50 values for B. suzhenae and B. bungaroides were 0.0133 μg/g and 0.752 μg/g, respectively, providing a reference for toxicity studies of these two species. This research elucidates the proteomic differences in the venoms of these two species, offering a foundation for developing antivenoms and clinical treatments for envenomation. Full article

Viperid snake venoms are notably abundant in metalloproteinases (proteins) (SVMPs), which are primarily responsible for inducing hemorrhage and disrupting the hemostatic process and tissue integrity in envenomed victims. In this study, barnettlysin-III (Bar-III), a hemorrhagic P-III SVMP, was purified from the venom of the Peruvian snake Bothrops barnetti. Bar-III has a molecular mass of approximately 50 kDa and is a glycosylation-dependent functional metalloproteinase. Some biochemical properties of Bar-III, including the full amino acid sequence deduced from its cDNA, are reported. Its enzymatic activity is increased by Ca²⁺ ions and inhibited by an excess of Zn²⁺. Synthetic metalloproteinase inhibitors and EDTA also inhibit its proteolytic action. Bar-III degrades several plasma and ECM proteins, including fibrin(ogen), fibronectin, laminin, and nidogen. Platelets play a key role in hemostasis and thrombosis and in other biological process, such as inflammation and immunity, and platelet activation is driven by the platelet signaling receptors, glycoprotein (GP)Ib-IX-V, which binds vWF, and GPVI, which binds collagen. Moreover, Bar-III inhibits vWF- and convulxin-induced platelet aggregation in human washed platelets by cleaving the recombinant A1 domain of vWF and GPVI into a soluble ectodomain fraction of ~55 kDa (sGPVI). Bar-III does not reduce the viability of cultured endothelial cells; however, it interferes with the adhesion of these cells to fibronectin, vitronectin, and RGD peptides, as well as their migration profile. Bar-III binds specifically to the surface of these cells, and part of this interaction involves α5β1 integrin receptors. These results contribute to a better comprehension of the pathophysiology of snakebite accidents/incidents and could be used as a tool to explore novel and safer anti-venom therapeutics. Full article

Snake venoms are cocktails of biologically active molecules that have evolved to immobilize prey, but can also induce a severe pathology in humans that are bitten. While animal-derived polyclonal antivenoms are the primary treatment for snakebites, they often have limitations in efficacy and can cause severe adverse side effects. Building on recent efforts to develop improved antivenoms, notably through monoclonal antibodies, requires a comprehensive understanding of venom toxins. Among these toxins, snake venom metalloproteinases (SVMPs) play a pivotal role, particularly in viper envenomation, causing tissue damage, hemorrhage and coagulation disruption. One of the current challenges in the development of neutralizing monoclonal antibodies against SVMPs is the large size of the protein and the lack of existing knowledge of neutralizing epitopes. Here, we screened a synthetic human antibody library to isolate monoclonal antibodies against an SVMP from saw-scaled viper (genus Echis) venom. Upon characterization, several antibodies were identified that effectively blocked SVMP-mediated prothrombin activation. Cryo-electron microscopy revealed the structural basis of antibody-mediated neutralization, pinpointing the non-catalytic cysteine-rich domain of SVMPs as a crucial target. These findings emphasize the importance of understanding the molecular mechanisms of SVMPs to counter their toxic effects, thus advancing the development of more effective antivenoms. Full article

Cloud data centers play a vital role in modern computing infrastructure, offering scalable resources for diverse applications. However, managing costs and resources efficiently in these centers has become a crucial concern due to the exponential growth of cloud computing. User applications exhibit complex behavior, leading to fluctuations in system performance and increased power usage. To tackle these obstacles, we introduce the Modified Feeding Birds Algorithm (ModAFBA) as an innovative solution for virtual machine (VM) consolidation in cloud environments. The primary objective is to enhance resource management and operational efficiency in cloud data centers. ModAFBA incorporates adaptive position update rules and strategies specifically designed to minimize VM migrations, addressing the unique challenges of VM consolidation. The experimental findings demonstrated substantial improvements in key performance metrics. Specifically, the ModAFBA method exhibited significant enhancements in energy usage, SLA compliance, and the number of VM migrations compared to benchmark algorithms such as TOPSIS, SVMP, and PVMP methods. Notably, the ModAFBA method achieved reductions in energy usage of 49.16%, 55.76%, and 65.13% compared to the TOPSIS, SVMP, and PVMP methods, respectively. Moreover, the ModAFBA method resulted in decreases of around 83.80%, 22.65%, and 89.82% in the quantity of VM migrations in contrast to the aforementioned benchmark techniques. The results demonstrate that ModAFBA outperforms these benchmarks by significantly reducing energy consumption, operational costs, and SLA violations. These findings highlight the effectiveness of ModAFBA in optimizing VM placement and consolidation, offering a robust and scalable approach to improving the performance and sustainability of cloud data centers. Full article

The protein profile of Bothrops rhombeatus venom was compared to Bothrops asper and Bothrops atrox, and the effectiveness of antivenoms from the National Institute of Health of Colombia (INS) and Antivipmyn-Tri (AVP-T) of Mexico were analyzed. Protein profiles were studied with sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and reverse-phase high-performance liquid chromatography (RP-HPLC). The neutralizing potency and the level of immunochemical recognition of the antivenoms to the venoms were determined using Western blot, affinity chromatography, and enzyme-linked immunosorbent assay (ELISA). Bands of phospholipase A2 (PLA2), metalloproteinases (svMPs) I, II, and III as well as serine proteinases (SPs) in the venom of B. rhombeatus were recognized by SDS-PAGE. With Western blot, both antivenoms showed immunochemical recognition towards PLA2 and svMP. INS showed 94% binding to B. rhombeatus venom and 92% to B. asper while AVP-T showed 90.4% binding to B. rhombeatus venom and 96.6% to B. asper. Both antivenoms showed binding to PLA2 and svMP, with greater specificity of AVP-T towards B. rhombeatus. Antivenom neutralizing capacity was calculated by species and mL of antivenom, finding the following for INS: B. asper 6.6 mgV/mL, B. atrox 5.5 mgV/mL, and B. rhombeatus 1.3 mgV/mL. Meanwhile, for AVP-T, the following neutralizing capacities were found: B. asper 2.7 mgV/mL, B. atrox 2.1 mgV/mL, and B. rhombeatus 1.4 mgV/mL. These results show that both antivenoms presented similarity between calculated neutralizing capacities in our trial, reported in a product summary for the public for the B. asper species; however, this does not apply to the other species tested in this trial. Full article

Viperid snake venoms induce severe tissue damage, characterized by the direct toxic action of venom components, i.e., phospholipases A₂ (PLA₂s) and metalloproteinases (SVMPs), concomitantly with the onset of endogenous inflammatory processes, in an intricate scenario of tissue alterations. Understanding the expression of relevant genes in muscle tissue will provide valuable insights into the undergoing pathological and inflammatory processes. In this study, we have used the Nanostring technology to evaluate the patterns of gene expression in mouse skeletal muscle 1 h, 6 h, and 24 h after injection of the venoms of Bothrops asper and Daboia russelii, two medically relevant species in Latin America and Asia, respectively, with somewhat different clinical manifestations. The dose of venoms injected (30 µg) induced local pathological effects and inflammation in muscle tissue. We focused our analysis on genes related to extracellular matrix (ECM) metabolism, immune system, programmed cell death, and autophagy. The results revealed a complex pattern of expression of genes. Regarding ECM metabolism and regulation, up-regulated genes included proteinase inhibitor Serpine 1, thrombospondin 1, collagens 1A1 and 4A1 (at 1 h in the case of B. asper), TIMP1, MMP-3 (at 24 h), and lysil oxidase (LOX). In contrast, collagen chains 5A3 and 5A1 were down-regulated, especially at 6 h. Transforming growth factor β (TGF-β) and several genes related to myofibroblast regulation were also up-regulated, which might be related to the development of fibrosis. Several genes related to cytokine and chemokine synthesis and regulation and NFκB signaling were also up-regulated. Our observations show a variable expression of genes associated with programmed cell death and autophagy, thus revealing a hitherto unknown role of autophagy in tissue affected by snake venoms. These results provide clues to understanding the complex pattern of gene expression in tissue affected by viperid snake venoms, which likely impacts the final pathophysiology of damaged tissue in envenomings. Full article

Naja nivea (N. nivea) is classed as a category one snake by the World Health Organization since its envenomation causes high levels of mortality and disability annually. Despite this, there has been little research into the venom composition of N. nivea, with only one full venom proteome published to date. Our current study separated N. nivea venom using size exclusion chromatography before utilizing a traditional bottom-up proteomics approach to unravel the composition of the venom proteome. As expected by its clinical presentation, N. nivea venom was found to consist mainly of neurotoxins, with three-finger toxins (3FTx), making up 76.01% of the total venom proteome. Additionally, cysteine-rich secretory proteins (CRISPs), vespryns (VESPs), cobra venom factors (CVFs), 5′-nucleotidases (5′NUCs), nerve growth factors (NGFs), phospholipase A2s (PLA₂), acetylcholinesterases (AChEs), Kunitz-type serine protease inhibitor (KUN), phosphodiesterases (PDEs), L-amino acid oxidases (LAAOs), hydrolases (HYDs), snake venom metalloproteinases (SVMPs), and snake venom serine protease (SVSP) toxins were also identified in decreasing order of abundance. Interestingly, contrary to previous reports, we find PLA₂ toxins in N. nivea venom. This highlights the importance of repeatedly profiling the venom of the same species to account for intra-species variation. Additionally, we report the first evidence of covalent protein complexes in N. nivea venom, which likely contribute to the potency of this venom. Full article

Venom components are invaluable in biomedical research owing to their specificity and potency. Many of these components exist in two genera of rattlesnakes, Crotalus and Sistrurus, with high toxicity and proteolytic activity variation. This review focuses on venom components within rattlesnakes, and offers a comparison and itemized list of factors dictating venom composition, as well as presenting their known characteristics, activities, and significant applications in biosciences. There are 64 families and subfamilies of proteins present in Crotalus and Sistrurus venom. Snake venom serine proteases (SVSP), snake venom metalloproteases (SVMP), and phospholipases A2 (PLA2) are the standard components in Crotalus and Sistrurus venom. Through this review, we highlight gaps in the knowledge of rattlesnake venom; there needs to be more information on the venom composition of three Crotalus species and one Sistrurus subspecies. We discuss the activity and importance of both major and minor components in biomedical research and drug development. Full article