Krait Venom Research Articles

Biogenic synthesis of AgNPs via polyherbal formulation: Mechanistic neutralization and toxicological impact on acetylcholinesterase from Bungarus sindanus venom.

This study aims to examine the biogenic production, characterization, and anti-acetylcholinesterase (AAChE) properties of polyherbal formulation PHF-extract-synthesized silver nanoparticles (PHF-AgNPs). The Elapidae snake Bungarus sindanus has extremely dangerous venom for humans and contains a high amount of AChE (acetylcholinesterase). Inhibiting AChE leads to acetylcholine buildup, affecting neurotransmission. The study tested silver nanoparticles as AChE inhibitors using kinetics. Their production was confirmed through ultraviolet (UV) spectrometry at 425 nm (SPR peak of 1.94), and stabilizing functional groups were identified via Fourier transform infrared spectroscopy (FT-IR). The average length of 20 nm was confirmed by analyzing the scanning electron microscopy (SEM) data. Energy-dispersive X-ray spectroscopy (EDX) identified silver as the primary component of PHF-AgNPs (26%). Statistical analysis showed that the activity of AChE in krait venom decreased by up to 45% and 37% at a given dose of ACh (0.5 mM) by PHF and AgNPs, respectively. Utilizing the Lineweaver-Burk plot for kinetic analysis, a competitive type of inhibition is found. RESEARCH HIGHLIGHTS: Successfully synthesized PHF-extract-induced silver nanoparticles (PHF-AgNPs) demonstrated through UV spectrometry and characterized as crystalline with an average size of 45 nm by X-ray diffraction. PHF-AgNPs effectively inhibited acetylcholinesterase (AChE), an enzyme critical in neurotransmission, reducing its activity in krait venom by up to 45% at certain concentrations. Kinetic analysis revealed that the inhibition mechanism of AChE by PHF-AgNPs is competitive, offering potential for therapeutic applications in neurologically related conditions.

Molecular Memory Micromotors for Fast Snake Venom Toxin Dynamic Detection.

The analysis and detection of snake venom toxins are a matter of great importance in clinical diagnosis for fast treatment and the discovery of new pharmaceutical products. Current detection methods have high associated costs and require the use of sophisticated bioreceptors, which in some cases are difficult to obtain. Herein, we report the synthesis of template-based molecularly imprinted micromotors for dynamic detection of α-bungarotoxin as a model toxin present in the venom of many-banded krait (Bungarus multicinctus). The specific recognition sites are built-in in the micromotors by incubation of the membrane template with the target toxin, followed by a controlled electrodeposition of a poly(3,4-ethylenedioxythiophene)/poly(sodium 4-styrenesulfonate) polymeric layer, a magnetic Ni layer to promote magnetic guidance and facilitate washing steps, and a Pt layer for autonomous propulsion in the presence of hydrogen peroxide. The enhanced fluid mixing and autonomous propulsion increase the likelihood of interactions with the target analyte as compared with static counterparts, retaining the tetramethylrhodamine-labeled α-bungarotoxin on the micromotor surface with extremely fast dynamic sensor response (after just 20 s navigation) in only 3 μL of water, urine, or serum samples. The sensitivity achieved meets the clinically relevant concentration postsnakebite (from 0.1 to 100 μg/mL), illustrating the feasibility of the approach for practical applications. The selectivity of the protocol is very high, as illustrated by the absence of fluorescence in the micromotor surface in the presence of α-cobratoxin as a representative toxin with a size and structure similar to those of α-bungarotoxin. Recoveries higher than 95% are obtained in the analysis of urine- and serum-fortified samples. The new strategy holds considerable promise for fast, inexpensive, and even onsite detection of several toxins using multiple molecularly imprinted micromotors with tailored recognition abilities.

Development of chicken egg yolk antibodies (IgY) against venom of cobra (Naja naja) and krait (Bungarus caeruleus) and a study on its neutralization potential

The Big Four snakes are the leading causes of snakebite mortality in India. Among them, The Indian spectacled cobra (Naja naja) and common krait (Bungarus caeruleus) contribute about one-third of the deaths. The conventional anti-snake venoms (ASV) produced from equine serum are found to be expensive, with a high frequency of clinical side effects, low specificity, and production drawbacks. The current study, therefore, attempted to develop chicken egg yolk immunoglobulins (IgY) as antivenoms against the venoms of cobra and krait venoms. The major pathophysiological properties of the venoms and the efficacy of monovalent ASV IgY were evaluated. The titer of anti-cobra and anti-krait IgY was found to be 1:64000 on the 145th day post-immunization. The results showed that venoms (lethal doses (LD50): cobra:0.375 mg/kg, krait:0.0375 mg/kg of mice) had hemolytic, pro-coagulant, inflammatory, hemorrhagic, and edematic activities that were effectively neutralized by ASV-IgY. 1 mL of monovalent ASV IgY was able to neutralize 0.22 mg of cobra venom and 0.028 mg of krait venom whereas 1 mL of commercial polyvalent antivenom was able to neutralize 0.28 mg of cobra venom and 0.035 mg of krait venom. The study results suggest that using chicken IgY as an monovalent antivenom could effectively treat snakebites.

Agonists of melatonin receptors strongly promote the functional recovery from the neuroparalysis induced by neurotoxic snakes.

Snake envenoming is a major, but neglected, tropical disease. Among venomous snakes, those inducing neurotoxicity such as kraits (Bungarus genus) cause a potentially lethal peripheral neuroparalysis with respiratory deficit in a large number of people each year. In order to prevent the development of a deadly respiratory paralysis, hospitalization with pulmonary ventilation and use of antivenoms are the primary therapies currently employed. However, hospitals are frequently out of reach for envenomated patients and there is a general consensus that additional, non-expensive treatments, deliverable even long after the snake bite, are needed. Traumatic or toxic degenerations of peripheral motor neurons cause a neuroparalysis that activates a pro-regenerative intercellular signaling program taking place at the neuromuscular junction (NMJ). We recently reported that the intercellular signaling axis melatonin-melatonin receptor 1 (MT1) plays a major role in the recovery of function of the NMJs after degeneration of motor axon terminals caused by massive Ca2+ influx. Here we show that the small chemical MT1 agonists: Ramelteon and Agomelatine, already licensed for the treatment of insomnia and depression, respectively, are strong promoters of the neuroregeneration after paralysis induced by krait venoms in mice, which is also Ca2+ mediated. The venom from a Bungarus species representative of the large class of neurotoxic snakes (including taipans, coral snakes, some Alpine vipers in addition to other kraits) was chosen. The functional recovery of the NMJ was demonstrated using electrophysiological, imaging and lung ventilation detection methods. According to the present results, we propose that Ramelteon and Agomelatine should be tested in human patients bitten by neurotoxic snakes acting presynaptically to promote their recovery of health. Noticeably, these drugs are commercially available, safe, non-expensive, have a long bench life and can be administered long after a snakebite even in places far away from health facilities.

Investigação e desenvolvimento de imunoensaios comparativos para produção de imunoglobulinas contra veneno da cobra (Bungarus sindanus) em aves

ABSTRACT: Present study aimed for detection, purification, quantification of Sind Krait (Bungarus sindanus) antivenom from chicken eggs and to determine extracted antivenom efficacy in mice. Hens’ three groups were immunized by sub-lethal doses of Sind Krait venom with adjuvant paraffin oil+lecithin. Booster doses were injected subcutaneously on pectorals muscles at multiple sites after every two weeks upto eight weeks. Antibodies-IgY produced against Sind Krait venom was purified form eggs’ yolk by precipitation method with PEG-6000. Purified antivenom-IgY protein contents were quantified by Nanodrop-photometer, purity accessed by SDS-PAGE, specificity checked by Ochterloneys method and titer estimated by indirect ELISA. Antivenom efficacy was assessed in albino mice. Purified antivnom-IgY exhibited single protein band 180-190 kDa on SDS-PAGE under non-reduced condition and two-bands 63 - 65 kDa and 22 - 25 kDa correspondingly under-reduced condition. Immunodiffusion exhibited sharp precipitation lines of immune-complex (venom and extracted-IgY). In all groups (G1, G2 and G3) antivenom level sharply increase from 3rd to 4th week and maintained thereafter. G2 and G3 presented high titer upto 1:2048 dilutions, while G1 showed upto 1:1024 dilutions, as tested by indirect ELISA. In neutralization assay ED50 dose of G2 and G3 obtained antivenom was 400.23 µg/mice for more than twofold LD50 dose of venom and 100% protection was at 508.84 µg/mice that completely neutralized highly lethal dose of venom. But G1 ED50 was 405.66 µg/mice and provides 100% protection at 554.21 µg/mice. Extracted antivenom, against Sind Krait venom were highly pure, and with high neutralization capacity were produced successfully from eggs yolk first time in Pakistan.

In silico Exploration of Bioactive Compounds from Withania somnifera as Inhibitor for Alpha Delta Bungarotoxin of Bungarus candidus Venom

The antivenom for Malayan krait (Bungarus candidus) venom has not yet been available in Indonesia, leading to many fatal snakebite cases. Alternative treatment approaches using medicinal plants are needed to be explored. This study investigated the potential of medicinal plants natural bioactive compounds as toxic alpha-delta protein bungarotoxin inhibitor in B. candidus venom. The approach taken is using the 3D structure of the alpha-delta protein of bungarotoxin B. candidus predicted by SWISS-MODEL. Knapsack Family Database and PubChem were used for bioactive compounds datamining.

The Potassium Channel Blocker β-Bungarotoxin from the Krait Bungarus multicinctus Venom Manifests Antiprotozoal Activity

Protozoal infections are a world-wide problem. The toxicity and somewhat low effectiveness of the existing drugs require the search for new ways of protozoa suppression. Snake venom contains structurally diverse components manifesting antiprotozoal activity; for example, those in cobra venom are cytotoxins. In this work, we aimed to characterize a novel antiprotozoal component(s) in the Bungarus multicinctus krait venom using the ciliate Tetrahymena pyriformis as a model organism. To determine the toxicity of the substances under study, surviving ciliates were registered automatically by an original BioLaT-3.2 instrument. The krait venom was separated by three-step liquid chromatography and the toxicity of the obtained fractions against T. pyriformis was analyzed. As a result, 21 kDa protein toxic to Tetrahymena was isolated and its amino acid sequence was determined by MALDI TOF MS and high-resolution mass spectrometry. It was found that antiprotozoal activity was manifested by β-bungarotoxin (β-Bgt) differing from the known toxins by two amino acid residues. Inactivation of β-Bgt phospholipolytic activity with p-bromophenacyl bromide did not change its antiprotozoal activity. Thus, this is the first demonstration of the antiprotozoal activity of β-Bgt, which is shown to be independent of its phospholipolytic activity.

Evaluation of Anti-Venom Potential of Areca catechu Seed Extract on Bungarus caeruleus Venom

Areca catechu seeds and their extract/s are currently used to treat various ailments and infections including snakebites. The purpose of this investigation was to assess the inhibiting/neutralizing effect of ethyl acetate and aqueous ethanolic seed extracts of A. catechu on Bungarus caeruleus (krait) venom. The enzyme activities and their inhibition were evaluated using standard procedures (in vitro). In vivo studies were conducted using chick embryos and murine models. The extracts inhibited hyaluronidase and phospholipase A2 activities. Protease activity was neutralized by the aqueous ethanolic extract only. The IC50 value of aqueous ethanolic extract for hyaluronidase was 0.001 g/mL, while that for the ethyl acetate extract for phospholipase A2 was 0.006 g/mL. In addition, both the extracts neutralized the indirect hemolysis and fibrinogenolytic activity induced by B. caeruleus venom. The LD50 for the chick embryos was 4.9 µg/egg. The 50 and 100 µg aqueous ethanolic extracts neutralized the LD50 and the challenging dose (3LD50) of venom effectively in the chick embryo model. The LD50 of B. caeruleus venom in mice was 0.1927 µg/kg; the extract extended the survival time of the mice from 25 min to 30 and 35 min in 1:10 and 1:20 ((w/w) venom:extract) ratios, respectively. The extract also neutralized myotoxic activity. The A. catechu seed extract showed promising inhibitory properties against B. caeruleus venom. In this regard, academia and industries should work collaboratively to develop and formulate a cost-effective first-aid drug.

New Synthesized Tri-Peptide as Inhibitor of Krait (Bungarus Sindanus) Venom Acetylcholinesterase

In the current study, the cyclopeptide alkaloid discarine D-derived tri-peptides fragments were synthesized and then investigated for their inhibitory potential against krait (Bungarus sindanus) venom acetylcholinesterase (AChE) enzyme. The tri-peptides L-Leu- threo-D-Pheser-L-Phe and L-Leu- threo-L-Pheser-L-Phe were chemically synthesized by a conventional method using the benzyloxycarbonyl group for the alpha-amino (α-amino) safety and the methyl esters an amino acids derivative used for the safety of carboxyl group. The present paper described that the general synthetic strategy of tri-peptide allows the tri-peptide sequence to be acquired with the N-terminal extreme protected. Kinetic studies using the Lineweaver Burk plot indicated that tri-peptides fragments cause an un-competitive type of inhibition i.e. both Km and Vmax values decreased with the increase of tri-peptides fragment concentration (13.5–22.5 µM). The estimated Ki and IC50 for krait venom AChE were found to be 17.5 µM and 19.5 µM, respectively. Thus the present paper, clarified that the freshly produced tri-peptides fragment can be deliberated as a beneficial mediator for the inhibition of krait venom AChE.

A Life-Threatening Incidence of Neurotoxic Indian Krait Snake Bite: A Case Report

The Indian Krait delivers one of the most lethal venoms compared to other Asian snakes. The venom of the common Krait comprises substantial neurotoxins that cause muscular paralysis. Significant snake bite incidence occurs in rural areas. The significant death rate caused by snake bites is seldomly reported in the medical literature. A 14-year-old adolescent girl was brought by her parents to the emergency department (ED) in an unconscious state. The patient reported swelling on her right hand with fang marks of a snake bite, sweating, and increased salivation. The primary therapeutic intervention was given to the patient and she was treated with intravenous anti-snake venom serum, antibiotics, and anti-epileptics during hospitalisation.

A Factor XIa Inhibitor Engineered from Banded Krait Venom Toxin: Efficacy and Safety in Rodent Models of Arterial and Venous Thrombosis.

Activated factor XI (FXIa) is an important antithrombotic drug target. Clinical and pre-clinical data have demonstrated that its inhibition attenuates thrombosis with minimal risk of excessive bleeding. We isolated Fasxiator from the venom of banded krait Bungarus fasciatus and subsequently engineered FasxiatorN17R,L19E, with improved affinity (Ki = 0.9 nM) and selectivity towards FXIa. Here, we assess the in vivo efficacy and bleeding risk of rFasxiatorN17R, L19E in pre-clinical animal models. Rats injected intravenously (i.v.) with bolus rFasxiatorN17R, L19E showed the specific in vivo attenuation of the intrinsic coagulation pathway, lasting for at least 60 min. We performed the in vivo dose-ranging experiments for rFasxiatorN17R, L19E as follows: FeCl3-induced carotid artery occlusion in rats (arterial thrombosis); inferior vena cava ligation in mice (venous thrombosis); tail bleeding time in both rats and mice (bleeding risk). Head-to-head comparisons were made using therapeutic dosages of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) for arterial and venous thrombosis, respectively. In the arterial thrombosis model, 2 mg/kg i.v. rFasxiatorN17R,L19E achieved a similar antithrombotic efficacy to that of UFH, with >3-fold lower bleeding time. In the venous thrombosis model, the 10 mg/kg subcutaneous (s.c.) injection of rFasxiatorN17R,L19E achieved similar efficacy and bleeding levels to those of LMWH enoxaparin. Overall, rFasxiatorN17R,L19E represents a promising molecule for the development of FXIa-targeting anticoagulants.

On characterizing the Red-headed Krait (Bungarus flaviceps) venom: Decomplexation proteomics, immunoreactivity and toxicity cross-neutralization by hetero-specific antivenoms

The Red-headed Krait (Bungarus flaviceps) is a medically important venomous snake species in Southeast Asia, while there is no specific antivenom available for its envenoming. This study investigated the venom composition through a decomplexation proteomic approach, and examined the immunoreactivity as well as cross-neutralization efficacy of two hetero-specific krait antivenoms, Bungarus candidus Monovalent Antivenom (BcMAV) and Bungarus fasciatus Monovalent Antivenom (BfMAV), against the venom of B. flaviceps from Peninsular Malaysia. A total of 43 non-redundant proteoforms belonging to 10 toxin families were identified in the venom proteome, which is dominated by phospholipases A2 including beta-bungarotoxin lethal subunit (56.20 % of total venom proteins), Kunitz-type serine protease inhibitors (19.40 %), metalloproteinases (12.85 %) and three-finger toxins (7.73 %). The proteome varied in quantitative aspect from the earlier reported Indonesian (Sumatran) sample, suggesting geographical venom variation. BcMAV and BfMAV were immunoreactive toward the B. flaviceps venom, with BcMAV being more efficacious in immunological binding. Both antivenoms cross-neutralized the venom lethality with varying efficacy, where BcMAV was more potent than BfMAV by ~13 times (normalized potency: 38.04 mg/g vs. 2.73 mg/g, defined as the venom amount completely neutralized by one-gram antivenom protein), supporting the potential utility of BcMAV for para-specific neutralization against B. flaviceps venom.

Pharmacokinetics and Pharmacodynamics of Avian Egg-Yolk Derived Pure Anti-Snake Venom in Healthy and Disease Animal-Model

The absence of Fc receptor binding, cost-effective production potential in large quantities in pure form, and better storage stability of avian immunoglobulin (IgY) advocate its therapeutic use as anti-snake venom (ASV). This study develops pure anti-neurotoxin (ANT- IgY) by immunizing White Leghorn hens with Cobra and Krait venoms for demonstrating antigen-antibody binding in vitro/in vivo. The purified IgY from immunized egg-yolk showed immunoprecipitation in Ouchterlony's Double Diffusion (ODD) experiment. For characterizing ANT-IgY distribution and clearance pattern, the study utilized an enzyme-linked immunosorbent assay (ELISA) in serum at different intervals following intravenous (IV) administration. The Kinetica 5.1 software estimated pharmacokinetic parameters, including half-life. The IgY showed a time-dependent elimination through the intestinal route in fecal matter. After conjugating with a fluorochrome-Vivotag-750S, injected the purified ANT-IgY intravenously into the healthy mice. Subsequently, captured live-animal images to demonstrate the distribution and elimination profile of the molecule. Intramuscular injection of fluorochrome-tagged venom created the envenomed mice model. The live-animal images demonstrated the quick mobilization of venom into vital tissues. Intravenous administration of tagged ANT-IgY in the envenomed model showed the movement of ASV to the tissues venom traffics. The observed pharmacological benefit promise scope of ASV-IgY for therapeutic use.

ASSESSMENT OF SNAKE ANTIVENOM ACTIVITY OF TAMARINDUS INDICA SEED COAT EXTRACT

Snakebite is a life-threatening medical emergency, and globally responsible for millions of deaths. In snakebites accidents only deaths are not a concern, it leads to more morbidities. Due to scanty healthcare facilities in rural areas of India, many people seek alternative treatment available in ethnic practices. Tamarindus Indica (TI) plant is rich in medicinal value and used to treat many diseases including snakebite treatment traditionally. In view of this TI seed coat extract (TISCE) was evaluated for antivenom activity. The phytochemical screening of TISCE was performed to understand its chemical composition. TISCE was evaluated for antivenom activity against Indian cobra venom (ICV), common krait venom (CKV), Russells viper venom (RVV), and saw-scaled viper venom (SCV) for phospholipase A2 (PLA-2), haemorrhagic in vitro and in vivo, procoagulant, proteolytic activity, and lethality studies. TISCE majorly contains saponins, glycosides, alkaloids, and phenolic compounds. Minimum indirect haemorrhagic dose (MIHD) observed for ICV (12.5 µg), CKV (5.0 µg),RVV (10.0 µg), and SVV (12.5 µg). TISCE inhibits the procoagulant activity of all venoms at a concentration of 18.0 µg. It also shows the neutralization of proteolytic enzymes of venom in a dose-dependent manner. A pre-incubated mixture containing five lethal dose 50 (LD50) of venom and TISCE was injected intravenously, all mice survived as venom neutralized by TISCE. The present study demonstrates the ability of TISCE to neutralize snake venom using suitable in vivo and in vitro methods. Further studies required to unravelling the specific active chemical constituent of TISCE that may used as novel alternative snakebite treatment. TISCE was able to prolong the deaths during the simulation study and may be used in the topical pharmaceutical formulation that will reduce local venom reactions causing much morbidity, which will collectively with Anti-snake venom (ASV), used to treat envenomed patients more effectively.

Clinical effects of the combination of Traditional Chinese and Western Medicines on coronavirus disease 2019: a systematic review and Meta-analysi.

To explore the clinical efficacy of the combination of Traditional Chinese and Western Medicines for the treatment of coronavirus disease 2019 (COVID-19). Studies were identified in six popular medical databases. Thirteen studies were included. The results showed that combined treatment with Traditional Chinese and Western Medicines can reduce the probability of progression from mild to severe disease [RR = 0.34, 95% confidence interval (CI) (0.18, 0.65)] (P = 0.001) and improve the clinical cure rate [RR = 0.17, 95% CI (0.05, 0.28)] (P = 0.004). The use of an integrated treatment strategy shortened the time to the remission of fever [WMD = －1.27, 95% CI (－1.67, －0.92)](P < 0.001) and improved the incidences of the disappearance of fever and fatigue [RR = 1.25, 95% CI (1.06, 1.47) (P = 0.007); RR = 1.49, 95% CI (1.13, 1.97) (P = 0.004)]. A combined treatment strategy is effective for COVID-19.

Complex target SELEX-based identification of DNA aptamers against Bungarus caeruleus venom for the detection of envenomation using a paper-based device

Complex target SELEX always have been an intriguing approach to the scientific community, as it offers the potential discovery of novel biomarkers. We herein successfully performed SELEX on Bungarus caeruleus venom to develop a panel of highly affine aptamers that specifically recognizes the B. caeruleus (common krait) venom and was able to discriminate the B. caeruleus venom from Cobra, Russell's, and Saw-scaled viper's venom. The aptamers generated against the crude venom also lead to the identification of the specific component of the venom, which is β-Bungarotoxin, a toxin uniquely present in the B. caeruleus venom. The best performing aptamer candidates were used as a molecular recognition element in a paper-based device and were able to detect as low as 2 ng krait venom in human serum background. The developed aptamer-based paper device can be used for potential point-of-care venom detection applications due to its simplicity and affordability.

Potential of herbal cocktail of medicinal plant extracts against ‘big four’ snake venoms from India

BackgroundVenomous snake bites cause acute medical emergencies and are fatal. India accounts for large proportion of snake-bite deaths globally. Medically important ‘BIG FOUR’ snakes of India are Bungarus caeruleus (krait), Naja naja (cobra), Echis carinatus (saw-scaled viper) and Daboia russelii (Russell's viper). Polyherbal formulations have been proved to be effective in treatment of diseases than a single formulation. Objective(s)To evaluate aqueous ethanolic extract cocktail of Azadirachata indica, Butea monosperma, Citrus limon, Clerodendrum serratum and Areca catechu for antidote potential against BIG FOUR venoms in ex vivo and in vivo model. Materials and methodsAnti-hemorrhagic and venom neutralization studies were performed in seven-day old chick embryo model for ex vivo studies. In vivo studies were performed using male Swiss albino mice for antivenom potential of herbal cocktail by performing anti-edematic, anti-hemorrhagic, anti-myotoxic activity, and venom neutralization. ResultsHerbal cocktail exhibited differential venom inhibition potential against four venoms tested. Hemorrhagic activity was completely neutralized by the herbal cocktail; myotoxic activities of krait and Russell's viper venom were neutralized; while anti-edematic activity was observed for krait and cobra venom. Herbal cocktail completely neutralized venom lethality (3∗LD50) of krait and saw-scaled viper venom. ConclusionInhibitions of various venom components of all four venoms suggests presence of phytochemicals in herbal cocktail with therapeutic properties. Further studies would help in the development of a formulation as a first-aid towards treatment of snake bite victims.

Paediatric cases of Ceylon krait (Bungarus ceylonicus) bites and some similar looking non-venomous snakebites in Sri Lanka: Misidentification and antivenom administration

Ceylon krait (Bungarus ceylonicus) of the family Elapidae is a highly venomous endemic species inhabiting in the wet zone and some parts of the intermediate climatic zones of Sri Lanka. Clinical records of its bites are rare and limited to five case reports in the literature. It is of interest to note that there are several non-venomous snakes in Sri Lanka having similar morphological appearance to kraits causing identification difficulties which lead to unnecessary and unindicated administration of antivenom. We report two paediatric cases of proven Ceylon krait bites and three adult patients with similar looking non-venomous snakebites. These children were 1½ and 13 years old and developed neuroparalysis without progressing to respiratory failure and recovered. Both the children were administered Indian polyvalent antivenom which has not developed against endemic Ceylon krait venom. The two adult patients also received antivenom due to the misidentification without clinical and laboratory evidence of envenoming.

Proteomics and neutralization of Bungarus multicinctus (Many-banded Krait) venom: Intra-specific comparisons between specimens from China and Taiwan

The Many-banded Krait (Bungarus multicinctus) is a medically important venomous snake in East Asia. This study investigated the venom proteomes of B. multicinctus from Guangdong, southern China (BM-China) and insular Taiwan (BM-Taiwan), and the neutralization activities of two antivenom products (produced separately in China and Taiwan) against the lethal effect of the venoms. The venom proteomes of both specimens contained similar toxin families, notwithstanding small variations in the subtypes and abundances of minor components. More than 90% of the total venom proteins belong to three-finger toxins (3FTx, including alpha-neurotoxins) and phospholipases A2 (PLA2, including beta-bungarotoxins), supporting their key involvement in the pathophysiology of krait envenomation which manifests as pre- and post-synaptic neurotoxicity. The venoms exhibited potent neurotoxic and lethal effects with extremely low i.v. LD50 of 0.027 μg/g (Bm-China) and 0.087 μg/g (Bm-Taiwan), respectively, in mice. Bungarus multicinctus monovalent antivenom (BMMAV) produced in China and Neuro bivalent antivenom (NBAV) produced in Taiwan were immunoreactive toward both venoms and their toxin fractions. The antivenoms neutralized the venom lethality variably, with BMMAV being more efficacious than NBAV by approximately two-fold. Findings suggest that the monovalent antivenom has a higher potency presumably due to its species-specificity toward the krait venom.

Kinetic and toxicological effects of synthesized palladium(II) complex on snake venom (Bungarus sindanus) acetylcholinesterase.

Background: The venom of the krait (Bungarus sindanus), an Elapidae snake, is highly toxic to humans and contains a great amount of acetylcholinesterase (AChE). The enzyme AChE provokes the hydrolysis of substrate acetylcholine (ACh) in the nervous system and terminates nerve impulse. Different inhibitors inactivate AChE and lead to ACh accumulation and disrupted neurotransmission.Methods: The present study was designed to evaluate the effect of palladium(II) complex as antivenom against krait venom AChE using kinetics methods.Results: Statistical analysis showed that krait venom AChE inhibition decreases with the increase of Pd(II) complex (0.025-0.05 µM) and exerted 61% inhibition against the AChE at a fixed concentration (0.5 mM) of ACh. Kinetic analysis using the Lineweaver Burk plot showed that Pd(II) caused a competitive inhibition. The compound Pd(II) complex binds at the active site of the enzyme. It was observed that K m (Michaelis-Menten constant of AChE-ACh into AChE and product) increased from 0.108 to 0.310 mM (45.74 to 318.35%) and V max remained constant with an increase of Pd(II) complex concentrations. In AChE K Iapp was found to increase from 0.0912 to 0.025 µM (29.82-72.58%) and did not affect the V maxapp with an increase of ACh from (0.05-1 mM). K i (inhibitory constant) was estimated to be 0.029 µM for snake venom; while the K m was estimated to be 0.4 mM. The calculated IC50 for Pd(II) complex was found to be 0.043 µM at constant ACh concentration (0.5 mM).Conclusions:The results show that the Pd(II) complex can be deliberated as an inhibitor of AChE.