Search Results (22)

Snakebite envenomation by Bothrops species is a neglected tropical disease and a major cause of local tissue damage and disability in Latin America. Antivenom therapy is effective against systemic effects but fails to prevent local myonecrosis, inflammation, and pain. This study evaluated photobiomodulation therapy (PBMT) using infrared (808 nm) alone or in combination with red (660 nm) laser in a murine model of Bothrops leucurus envenomation. A single PBMT session was applied, and animals were evaluated at 24 and 72 h. Combined treatment significantly reduced edema, hyperthermia, plasma CK and LDH, restored nociceptive thresholds, and improved motor recovery compared with infrared alone. Principal component analysis demonstrated clustering of combined-treatment animals with negative controls, supporting a synergistic therapeutic effect. These findings highlight dual-wavelength PBMT as a promising adjunctive approach to antivenom, directly targeting local venom-induced pathology. Full article

The larvae of some lampyrid beetles are highly specialized predators of snails. They have been observed to climb on the shells of their prey and use this exposed position to bite and inject secretions potentially originating from the midgut. Besides serving the purpose of extra-oral digestion (EOD), injected compounds also seem to have a paralyzing effect. Up to now, the toxins causing this paralyzing activity have not been identified. In the current study, we provide a first compositional analysis of the midgut secretion from lampyrid larvae, with a focus on identifying putative neurotoxins causing the observed paralyzing effect. For this purpose, we utilized a combined proteo-transcriptomic approach to characterize the compounds present in the midgut secretion of larval stages of Lampyris noctiluca. In terms of the absolute numbers of identified compounds, the midgut secretion is dominated by hydrolyzing enzymes comprising peptidases, carboxylesterases, and glycosidases. However, when considering expression levels, a few rather short cysteine-rich peptides exceed all other compounds. Some of these compounds show moderate similarity to putative neurotoxins identified in the venom of other arthropods and could be responsible for paralyzing effects. In addition to these potential toxins, we provide a list of peptides typical of the midgut secretion of L. noctiluca, supplemented by the corresponding precursor sequences. Full article

In submitting conference proceedings to the 1st International Symposium on Research in Venomous Animals, Manaus, Brazil, 2–5 May 2023, the volume editors of the proceedings certify to the publisher that all abstracts published in this volume have been subjected to peer review, performed by a scientific committee administered by the volume editors [...] Full article

Snake venoms constitute a complex, rapidly evolving trait, whose composition varies between and within populations depending on geographical location, age and preys (diets). These factors have determined the adaptive evolution for predatory success and link venom heterogeneity with prey specificity. Moreover, understanding the evolutionary drivers of animal venoms has streamlined the biodiscovery of venom-derived compounds as drug candidates in biomedicine and biotechnology. The king cobra (Ophiophagus hannah; Cantor, 1836) is distributed in diverse habitats, forming independent populations, which confer differing scale markings, including between hatchlings and adults. Furthermore, king cobra venoms possess unique cytotoxic properties that are used as a defensive trait, but their toxins may also have utility as promising anticancer-agent candidates. However, the impact of geographical distribution and age on these potential venom applications has been typically neglected. In this study, we hypothesised that ontogenetic venom variation accompanies the morphological distinction between hatchlings and adults. We used non-transformed neonatal foreskin (NFF) fibroblasts to examine and compare the variability of venom cytotoxicity between adult captive breeding pairs from Malaysian and Chinese lineages, along with that of their progeny upon hatching. In parallel, we assessed the anticancer potential of these venoms in human-melanoma-patient-derived cells (MM96L). We found that in a geographical distribution and gender-independent manner, venoms from hatchlings were significantly less cytotoxic than those from adults (NFF; ~Log EC₅₀: 0.5–0.6 vs. 0.2–0.35 mg/mL). This is consistent with neonates occupying a semifossorial habitat, while adults inhabit more above-ground habitats and are therefore more conspicuous to potential predators. We also observed that Malaysian venoms exhibited a slightly higher cytotoxicity than those from the Chinese cobra cohorts (NFF; Log EC₅₀: 0.1–0.3 vs. 0.3–0.4 mg/mL), which is consistent with Malaysian king cobras being more strongly aposematically marked. These variations are therefore suggestive of differential anti-predator strategies associated with the occupation of distinct niches. However, all cobra venoms were similarly cytotoxic in both melanoma cells and fibroblasts, limiting their potential medical applications in their native forms. Full article

Snake envenomation remains an important yet neglected medical problem in many countries, with around five million people affected, and over a hundred thousand deaths annually. Plasma-derived antivenoms are the main therapeutic agent available. Monovalent antivenoms are produced via the immunization of large animals, e.g., horses, with one venom, after which the horse serum can neutralize the homologous venom, with minimal or no cross neutralization against other venoms. It is necessary, therefore, for the culprit snake to be identified, so that the appropriate specific antivenom can be selected. Polyvalent antivenoms (pAVs) are produced via immunization with a number of snake venoms, and the serum can neutralize all the venoms used in its production. Thus, pAVs can be used to treat several venoms from a country/region, and the identification of the culprit snake is not necessary. There are various parameters and processes involved in the production of pAVs, depending on the requirements and resources available. Most commercial pAVs use a mixture of both elapid and viperid venoms as immunogens, while some pAVs use either elapid or viperid venoms. Some pAVs are produced through the mixing of more than one monovalent or polyvalent antivenom. These various types of pAVs have their own characteristics, and have benefits and drawbacks. The major benefits of pAVs are the wide coverage of many medically important venoms, including many heterologous venoms. They also remove the need to identify the culprit snake, and they can be produced at a lower cost than several monovalent antivenoms. Interesting polyvalent antivenoms, termed ‘syndromic pAVs’ (s-pAVs), have recently gained attention. They are produced for use according to the syndromes manifested in snakebite patients. The venoms that produce these syndromes are used as immunogens in the production of ‘syndromic antivenoms’. For example, ‘neurotoxic polyvalent antivenom’ and ‘hematotoxic polyvalent antivenom’ are produced using the neurotoxic elapid and hematotoxic viperid venoms as immunogens, respectively. They were first marketed by the Thai Red Cross in 2012, and have since gained attention as a possible therapeutic modality to help solve the problem of snakebite envenomation globally. The merits of these s-pAVs, including their efficacy and wide paraspecificities, are discussed. Full article

The Amazon represents the world’s greatest biodiversity and covers different countries in South America, including Brazil with the largest area. The interaction between the resident population of this area and its ecosystem is responsible for an intense exposure to venomous animals, which are considered an important health issue in the region. Therefore, the 1st International Symposium on Research in Venomous Animals, held from 2 May to 5 May 2023 in the city of Manaus in the state of Amazonas in Brazil, aimed to address animal envenomation aspects in the Brazilian Amazon and the exchange of ideas and knowledge between research groups from around the world. The event was attended by graduate students as well as renowned researchers from the Americas, Europe, and Asia. The event presented a multidisciplinary and translational approach in the area of toxinology, including themes such as clinical envenomation (clinical management, pathophysiology, and public policy strategies), preclinical studies, biological aspects of venomous animals’ venoms (venom composition/variation and geographical distribution), interdisciplinary studies on health anthropology and economics, and bioprospecting aspects (toxins with therapeutic and/or technological potential). Full article

Snakebite envenoming is a neglected tropical disease (NTD) that results from the injection of snake venom of a venomous snake into animals and humans. In Africa (mainly in sub-Saharan Africa), over 100,000 envenomings and over 10,000 deaths per annum from snakebite have been reported. Difficulties in snakebite prevention and antivenom treatment are believed to result from a lack of epidemiological data and underestimated figures on snakebite envenoming-related morbidity and mortality. There are species- and genus-specific variations associated with snake venoms in Africa and across the globe. These variations contribute massively to diverse differences in venom toxicity and pathogenicity that can undermine the efficacy of adopted antivenom therapies used in the treatment of snakebite envenoming. There is a need to profile all snake venom proteins of medically important venomous snakes endemic to Africa. This is anticipated to help in the development of safer and more effective antivenoms for the treatment of snakebite envenoming within the continent. In this review, the proteomes of 34 snake venoms from the most medically important snakes in Africa, namely the Viperidae and Elipdae, were extracted from the literature. The toxin families were grouped into dominant, secondary, minor, and others based on the abundance of the protein families in the venom proteomes. The Viperidae venom proteome was dominated by snake venom metalloproteinases (SVMPs–41%), snake venom serine proteases (SVSPs–16%), and phospholipase A₂ (PLA₂–17%) protein families, while three-finger toxins (3FTxs–66%) and PLA₂s (16%) dominated those of the Elapidae. We further review the neutralisation of these snake venoms by selected antivenoms widely used within the African continent. The profiling of African snake venom proteomes will aid in the development of effective antivenom against snakebite envenoming and, additionally, could possibly reveal therapeutic applications of snake venom proteins. Full article

Snakebite envenomation is considered a neglected tropical disease, affecting tens of thousands of people each year. The recommended treatment is the use of antivenom, which is composed of immunoglobulins or immunoglobulin fragments obtained from the plasma of animals hyperimmunized with one (monospecific) or several (polyspecific) venoms. In this review, the efforts made in the improvement of the already available antivenoms and the development of new antivenoms, focusing on snakes of medical importance from sub-Saharan Africa and Latin America, are described. Some antivenoms currently used are composed of whole IgGs, whereas others use F(ab’)2 fragments. The classic methods of attaining snake antivenoms are presented, in addition to new strategies to improve their effectiveness. Punctual changes in immunization protocols, in addition to the use of cross-reactivity between venoms from different snakes for the manufacture of more potent and widely used antivenoms, are presented. It is known that venoms are a complex mixture of components; however, advances in the field of antivenoms have shown that there are key toxins that, if effectively blocked, are capable of reversing the condition of in vivo envenomation. These studies provide an opportunity for the use of monoclonal antibodies in the development of new-generation antivenoms. Thus, monoclonal antibodies and their fragments are described as a possible alternative for the production of antivenoms, regardless of the venom. This review also highlights the challenges associated with their development. Full article

Venom is a dynamic trait that has contributed to the success of numerous organismal lineages. Predominantly composed of proteins, these complex cocktails are deployed for predation and/or self-defence. Many non-toxic physiological proteins have been convergently and recurrently recruited by venomous animals into their toxin arsenal. Phospholipase A₂ (PLA₂) is one such protein and features in the venoms of many organisms across the animal kingdom, including snakes of the families Elapidae and Viperidae. Understanding the evolutionary history of this superfamily would therefore provide insight into the origin and diversification of venom toxins and the evolution of novelty more broadly. The literature is replete with studies that have identified diversifying selection as the sole influence on PLA₂ evolution. However, these studies have largely neglected the structural/functional constraints on PLA₂s, and the ecology and evolutionary histories of the diverse snake lineages that produce them. By considering these crucial factors and employing evolutionary analyses integrated with a schema for the classification of PLA₂s, we uncovered lineage-specific differences in selection regimes. Thus, our work provides novel insights into the evolution of this major snake venom toxin superfamily and underscores the importance of considering the influence of evolutionary and ecological contexts on molecular evolution. Full article

Snakebite envenomation is a neglected tropical disease that causes over 100,000 deaths each year. The only effective treatment consists of antivenoms derived from animal sera, but these have been deemed with highly variable potency and are usually inaccessible and too costly for victims. The production of antivenoms by venom-independent techniques, such as the immunization with multi-epitope constructs, could circumvent those drawbacks. Herein, we present a knowledge-based pipeline to prioritize potential epitopes of therapeutic relevance from toxins of medically important snakes in West Sub-Saharan Africa. It is mainly based on sequence conservation and protein structural features. The ultimately selected 41 epitopes originate from 11 out of 16 snake species considered of highest medical importance in the region and 3 out of 10 of those considered as secondary medical importance. Echis ocellatus, responsible for the highest casualties in the area, would be covered by 12 different epitopes. Remarkably, this pipeline is versatile and customizable for the analysis of snake venom sequences from any other region of the world. Full article

Animal venoms offer a valuable source of potent new drug leads, but their mechanisms of action are largely unknown. We therefore developed a novel network pharmacology approach based on multi-omics functional data integration to predict how stingray venom disrupts the physiological systems of target animals. We integrated 10 million transcripts from five stingray venom transcriptomes and 848,640 records from three high-content venom bioactivity datasets into a large functional data network. The network featured 216 signaling pathways, 29 of which were shared and targeted by 70 transcripts and 70 bioactivity hits. The network revealed clusters for single envenomation outcomes, such as pain, cardiotoxicity and hemorrhage. We carried out a detailed analysis of the pain cluster representing a primary envenomation symptom, revealing bibrotoxin and cholecystotoxin-like transcripts encoding pain-inducing candidate proteins in stingray venom. The cluster also suggested that such pain-inducing toxins primarily activate the inositol-3-phosphate receptor cascade, inducing intracellular calcium release. We also found strong evidence for synergistic activity among these candidates, with nerve growth factors cooperating with the most abundant translationally-controlled tumor proteins to activate pain signaling pathways. Our network pharmacology approach, here applied to stingray venom, can be used as a template for drug discovery in neglected venomous species. Full article

Among the vast repertoire of animal toxins and venoms selected by nature and evolution, mankind opted to devote its scientific attention—during the last century—to a restricted group of animals, leaving a myriad of toxic creatures aside. There are several underlying and justifiable reasons for this, which include dealing with the public health problems caused by envenoming by such animals. However, these studies became saturated and gave rise to a whole group of animals that become neglected regarding their venoms and secretions. This repertoire of unexplored toxins and venoms bears biotechnological potential, including the development of new technologies, therapeutic agents and diagnostic tools and must, therefore, be assessed. In this review, we will approach such topics through an interconnected historical and scientific perspective that will bring up the major discoveries and innovations in toxinology, achieved by researchers from the Butantan Institute and others, and describe some of the major research outcomes from the study of these neglected animals. Full article

An estimated 15% of animals are venomous, with representatives spread across the majority of animal lineages. Animals use venoms for various purposes, such as prey capture and predator deterrence. Humans have always been fascinated by venomous animals in a Janus-faced way. On the one hand, humans have a deeply rooted fear of venomous animals. This is boosted by their largely negative image in public media and the fact that snakes alone cause an annual global death toll in the hundreds of thousands, with even more people being left disabled or disfigured. Consequently, snake envenomation has recently been reclassified by the World Health Organization as a neglected tropical disease. On the other hand, there has been a growth in recent decades in the global scene of enthusiasts keeping venomous snakes, spiders, scorpions, and centipedes in captivity as pets. Recent scientific research has focussed on utilising animal venoms and toxins for the benefit of humanity in the form of molecular research tools, novel diagnostics and therapeutics, biopesticides, or anti-parasitic treatments. Continued research into developing efficient and safe antivenoms and promising discoveries of beneficial effects of animal toxins is further tipping the scales in favour of the “cure” rather than the “curse” prospect of venoms. Full article

Venomousness is a complex functional trait that has evolved independently many times in the animal kingdom, although it is rare among mammals. Intriguingly, most venomous mammal species belong to Eulipotyphla (solenodons, shrews). This fact may be linked to their high metabolic rate and a nearly continuous demand of nutritious food, and thus it relates the venom functions to facilitation of their efficient foraging. While mammalian venoms have been investigated using biochemical and molecular assays, studies of their ecological functions have been neglected for a long time. Therefore, we provide here an overview of what is currently known about eulipotyphlan venoms, followed by a discussion of how these venoms might have evolved under ecological pressures related to food acquisition, ecological interactions, and defense and protection. We delineate six mutually nonexclusive functions of venom (prey hunting, food hoarding, food digestion, reducing intra- and interspecific conflicts, avoidance of predation risk, weapons in intraspecific competition) and a number of different subfunctions for eulipotyphlans, among which some are so far only hypothetical while others have some empirical confirmation. The functions resulting from the need for food acquisition seem to be the most important for solenodons and especially for shrews. We also present several hypotheses explaining why, despite so many potentially beneficial functions, venomousness is rare even among eulipotyphlans. The tentativeness of many of the arguments presented in this review highlights our main conclusion, i.e., insights regarding the functions of eulipotyphlan venoms merit additional study. Full article

Slow lorises are enigmatic animal that represent the only venomous primate lineage. Their defensive secretions have received little attention. In this study we determined the full length sequence of the protein secreted by their unique brachial glands. The full length sequences displayed homology to the main allergenic protein present in cat dander. We thus compared the molecular features of the slow loris brachial gland protein and the cat dander allergen protein, showing remarkable similarities between them. Thus we postulate that allergenic proteins play a role in the slow loris defensive arsenal. These results shed light on these neglected, novel animals. Full article