ADDovenom: Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming.

Snakebite envenoming can be a life-threatening medical emergency that requires prompt medical intervention to neutralise the effects of venom toxins. Each year up to 138,000 people die from snakebites and threefold more victims suffer life-altering disabilities. The current treatment of snakebite relies solely on antivenom-polyclonal antibodies isolated from the plasma of hyperimmunised animals-which is associated with numerous deficiencies.

Multiple biomarkers response of Astyanax lacustris (Teleostei: Characidae) exposed to manganese and temperature increase.

The present study aimed to evaluate the toxicity of Mn (6.65 mg/L) at different exposure times (96 h, 7, 14, and 21 days) and evaluate its possible toxic effects on the fish Astyanax lacustris through multi-biomarkers and the maximum critical temperature (CT Max). The results show an increase in the Mn accumulation (liver and gills) with increasing exposure time.

Heterologous expression of Ts8, a neurotoxin from Tityus serrulatus venom, evidences its antifungal activity.

In this study we expressed the Ts8, a neurotoxin from Tityus serrulatus scorpion venom, in Pichia pastoris yeast. We evaluated the peptide expression in different conditions, such as pH, temperature, and addition of casamino acids supplement. Analyses of expressed products by mass spectrometry and Edman degradation showed that rTs8 has sites that allow its cleavage by yeast proteases released into the culture medium.

Gene expression changes in Epinephelus marginatus (Teleostei, Serranidae) liver reveals candidate molecular biomarker of iron ore contamination.

Wastes from iron ore mining activities are potentially damaging to adjacent aquatic ecosystems. We aimed to determine biomarkers of environmental exposure to this xenobiotic in the dusky grouper Epinephelus marginatus by differential gene expression analysis. For this, fish were exposed to iron ore (15.

Dry heat and pressure favor bioactive compounds preservation and peptides formation in sorghum [ (L.) Moench].

Sorghum is a cereal with potential economic and nutritional properties. It has gained headway in the international market because of its nutritional content which is characterized for many bioactive compounds with antioxidant characteristics, and also, because it is gluten free. This work evaluated the proteomic profile of sorghum grains and its nutritional composition and functional profile after exposure to 7 different treatments (control, grind, dry heat, bursting, wet cooking with and without water and wet cooking in pressure).

Towards toxin PEGylation: The example of rCollinein-1, a snake venom thrombin-like enzyme, as a PEGylated biopharmaceutical prototype.

PEGylation was firstly described around 50 years ago and has been used for more than 30 years as a strategy to improve the drugability of biopharmaceuticals. However, it remains poorly employed in toxinology, even though it may be a promising strategy to empower these compounds in therapeutics. This work reports the PEGylation of rCollinein-1, a recombinant snake venom serine protease (SVSP), able to degrade fibrinogen and inhibit the hEAG1 potassium channel.

Gene Expression Changes in Epinephelus marginatus (Teleostei, Serranidae) Liver as Molecular Biomarker of Iron Ore Contamination.

The aim of this study was to determine selected molecular biomarkers of iron ore contamination in Epinephelus marginatus. Molecular biomarkers were tested by checking the relative expression of genes involved in oxidative stress, trace element regulation, and cellular damage, by RT-qPCR. Iron ore exposure caused the downregulation of ferroportin (FP) gene expression and a significant upregulation in superoxide dismutase (SOD) and cytochrome P450 1A (CYP1A) genes.

De novo assembly and annotation of the transcriptome of Astyanax lacustris liver unveil candidate genes to monitor response to environmental stress.

Astyanax lacustris is a freshwater characid fish species that inhabits small streams, lakes and rivers in South America. These fish are abundant in the wild and highly adaptable in captive, being considered a good model for ecotoxicological studies. Nevertheless, there are only shortcoming gene sequence information available in public databases, which hinder their use in more comprehensive investigations that employ sensitivity molecular biology techniques to assess gene expression profile for biomarker identification.

From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery.

Animal poisons and venoms are comprised of different classes of molecules displaying wide-ranging pharmacological activities. This review aims to provide an in-depth view of toxin-based compounds from terrestrial and marine organisms used as diagnostic tools, experimental molecules to validate postulated therapeutic targets, drug libraries, prototypes for the design of drugs, cosmeceuticals, and therapeutic agents. However, making these molecules applicable requires extensive preclinical trials, with some applications also demanding clinical trials, in order to validate their molecular target, mechanism of action, effective dose, potential adverse effects, as well as other fundamental parameters.

Beyond hemostasis: a snake venom serine protease with potassium channel blocking and potential antitumor activities.

Snake venom serine proteases (SVSPs) are complex and multifunctional enzymes, acting primarily on hemostasis. In this work, we report the hitherto unknown inhibitory effect of a SVSP, named collinein-1, isolated from the venom of Crotalus durissus collilineatus, on a cancer-relevant voltage-gated potassium channel (hEAG1). Among 12 voltage-gated ion channels tested, collinein-1 selectively inhibited hEAG1 currents, with a mechanism independent of its enzymatic activity.

Geophagus brasiliensis (Teleostei: Cichlidae) as an indicator of toxicity of ornamental stone processing wastes.

Massive exploitation of geological resources may lead to environmental issues due to the inadequate disposal of the processing wastes, which are potentially hazard to terrestrial and aquatic environments. To evaluate the toxic effects ornamental stones processing wastes (OSPW), Geophagus brasiliensis fish were contaminated with different concentrations of OSPW (250, 500, 750 and 1000 mg/L). The contaminated aquarium water showed increased total hardness and Ca, Na, K, Mg and Mn content, which lead to bioconcentration of Na, K and Mg in G.

Toxic effects of ornamental stone processing waste effluents on Geophagus brasiliensis (Teleostei: Cichlidae).

The ornamental stone industry generates considerable amounts of waste (OSPW), which may eventually reach natural environments and impact the local ecosystem. The aim of this study was to compare the toxic effects of two OSPW effluents in Geophagus brasiliensis: i) leachate effluent from a lagoon in an OSPW landfill (LE) and ii) decanted effluent from an ornamental stone processing industry (DE). G.

First report on BaltCRP, a cysteine-rich secretory protein (CRISP) from Bothrops alternatus venom: Effects on potassium channels and inflammatory processes.

CRISPs represent a family of cysteine-rich secretory proteins with molecular mass between 20 and 30 kDa and a highly conserved specific pattern of 16 cysteine residues. In this work, we isolated and characterized a novel CRISP from Bothrops alternatus venom, named BaltCRP, also evaluating its effects on different isoforms of potassium channels (Kv1.1; Kv1.

Functional and biological insights of rCollinein-1, a recombinant serine protease from .

Background: The prevalent class of snake venom serine proteases (SVSP) in Viperidae venoms is the thrombin-like enzymes, which, similarly to human thrombin, convert fibrinogen into insoluble fibrin monomers. However, thrombin-like serine proteases differ from thrombin by being unable to activate factor XIII, thus leading to the formation of loose clots and fibrinogen consumption. We report the functional and biological characterization of a recombinant thrombin-like serine protease from , named rCollinein-1.

Microbial production of toxins from the scorpion venom: properties and applications.

Scorpion venom are composed mainly of bioactive proteins and peptides that may serve as lead compounds for the design of biotechnological tools and therapeutic drugs. However, exploring the therapeutic potential of scorpion venom components is mainly impaired by the low yield of purified toxins from milked venom. Therefore, production of toxin-derived peptides and proteins by heterologous expression is the strategy of choice for research groups and pharmaceutical industry to overcome this limitation.

Global proteomic and functional analysis of Crotalus durissus collilineatus individual venom variation and its impact on envenoming.

Individual variations studies are important to understand the snakebite envenoming and to improve the antivenom production and its effectiveness. In this way, the objective of this study was a comparative analysis of intraspecific variation in the venom composition of 22 Crotalus durissus collilineatus specimens through proteomic techniques. Venoms were fractionated by RP-FPLC, and analyzed by SDS-PAGE and mass spectrometry.

Heterologous expression of rTsHyal-1: the first recombinant hyaluronidase of scorpion venom produced in Pichia pastoris system.

In general, hyaluronidases have a broad potential application on medicine and esthetics fields. Hyaluronidases from animal venoms cleave hyaluronan present in the extracellular matrix, acting as spreading factors of toxins into the tissues of the victim. However, the in-depth characterization of hyaluronidase from animal venoms has been neglected due to its instability and low concentration in the venom, which hamper its isolation.

LmrBPP9: A synthetic bradykinin-potentiating peptide from Lachesis muta rhombeata venom that inhibits the angiotensin-converting enzyme activity in vitro and reduces the blood pressure of hypertensive rats.

Bradykinin-potentiating peptides (BPPs) are an important group of toxins present in Lachesis muta rhombeata venom. They act directly at renin-angiotensin-aldosterone system, through the inhibition of angiotensin-converting enzyme (ACE). This action may contribute to the hypotensive shock observed during the envenoming by this species.

Minor snake venom proteins: Structure, function and potential applications.

Snake venoms present a great diversity of pharmacologically active compounds that may be applied as research and biotechnological tools, as well as in drug development and diagnostic tests for certain diseases. The most abundant toxins have been extensively studied in the last decades and some of them have already been used for different purposes. Nevertheless, most of the minor snake venom protein classes remain poorly explored, even presenting potential application in diverse areas.

Expression and partial biochemical characterization of a recombinant serine protease from Bothrops pauloensis snake venom.

Snake venom serine proteases (SVSPs) are enzymes capable of interfering at several points of hemostasis. Some serine proteases present thrombin-like activity, which makes them targets for the development of therapeutics agents in the treatment of many hemostatic disorders. In this study, a recombinant thrombin-like serine protease, denominated rBpSP-II, was obtained from cDNA of the Bothrops pauloensis venom gland and was characterized enzymatically and biochemically.

rBaltMIP, a recombinant alpha-type myotoxin inhibitor from Bothrops alternatus (Rhinocerophis alternatus) snake, as a potential candidate to complement the antivenom therapy.

Phospholipase A inhibitors (PLIs) are important targets in the search and development of new drugs. This study aimed at evaluating the potential of an alpha-type phospholipase A inhibitor from Bothrops alternatus (Rhinocerophis alternatus) snake in its recombinant form (rBaltMIP) to complement the conventional antivenom therapy. Biochemical experiments showed that rBaltMIP presented pI 5.

PEGylation: a successful approach to improve the biopharmaceutical potential of snake venom thrombin-like serine protease.

PEGylation is considered a successful technique to enhance the therapeutic and biotechnological potentials of peptides, proteins, toxins and drugs. The conjugation of polyethylene glycol (PEG) increases the size and molecular weight of conjugated molecule and improves its pharmacokinetics and pharmacodinamics by increasing water solubility, protecting from enzymatic degradation, reducing renal clearance and limiting immunogenic and antigenic reactions. These features are very useful for therapeutic proteins, since PEGylated proteins exhibit high stability and very low immunogenicity, ensuring a sustained clinical response with minimal dose and less frequent administration.

Expression of a new serine protease from Crotalus durissus collilineatus venom in Pichia pastoris and functional comparison with the native enzyme.

Snake venom serine proteases (SVSPs) act primarily on plasma proteins related to blood clotting and are considered promising for the treatment of several hemostatic disorders. We report the heterologous expression of a serine protease from Crotalus durissus collilineatus, named collinein-1, in Pichia pastoris, as well as the enzymatic comparative characterization of the toxin in native and recombinant forms. The complementary DNA (cDNA) encoding collinein-1 was amplified from cDNA library of C.

A New Phospholipase A₂ from Lachesis muta rhombeata: Purification, Biochemical and Comparative Characterization with Crotoxin B.

Phospholipases A2 (PLA2s) are enzymes responsible for inflammatory effects, edema formation, myotoxicity, neurotoxicity and other manifestations from envenoming. In this paper we report the isolation and biochemical characterization of Lmr-PLA2, the first acidic PLA2 found in Lachesis muta rhombeata venom. Furthermore, this study compared biological effects of Lmr-PLA2 and crotoxin B (CB), a PLA2 from Crotalus durissus terrificus venom.

Heterologous expression and biochemical and functional characterization of a recombinant alpha-type myotoxin inhibitor from Bothrops alternatus snake.

Venomous and non-venomous snakes possess phospholipase A2 (PLA2) inhibitory proteins (PLIs) in their blood serum. This study shows the expression and biochemical and functional characterization of a recombinant alpha inhibitor from Bothrops alternatus snake, named rBaltMIP. Its expression was performed in Pichia pastoris heterologous system, resulting in an active recombinant protein.