TL;DR: Three minor neurotoxic components that are present at levels of 1% or less in the Naja naja siamensis venom are also described, and one of the latter toxins appears to be nearly identical to the cobrotoxin of Nja naja atra venom.
Abstract: The principal neurotoxins of two commercial (Miami Serpentarium) preparations of venom from Naja naja siamensis, or Thailand cobra, and Naja naja naja, or spectacled Indian cobra, are isolated rapidly and simply by ion exchange chromatography on short (20–30 cm) columns of Bio-Rex 70 (or IRC-50) in volatile ammonium acetate buffers, followed by gel filtration on Sephadex G-50.
The Naja naja siamensis preparation contains a single principal neurotoxin that accounts for about one-fourth of the weight of the lyophilized crude venom, or one-third of the total venom protein. The Naja naja naja venom preparation contains approximately equal amounts of two principal neurotoxins which together account for more than one-fourth of the total venom protein.
The three principal neurotoxins contain 71 amino acids in a single peptide chain cross-linked by five disulfide bridges. The two Naja naja naja neurotoxins appear to differ only by a serine/isoleucine substitution, while both appear to differ from the principal Naja naja siamensis toxin only by two additional replacements: arginine for lysine and glycine for alanine.
Three minor neurotoxic components that are present at levels of 1% or less in the Naja naja siamensis venom are also described. One of these is a 61 amino acid toxin containing four disulfide bridges and two residues of tryptophan. The other two contain 62 amino acids and four disulfide bridges. One of the latter toxins appears to be nearly identical to the cobrotoxin of Naja naja atra venom.
TL;DR: Cobra factor, a protein of the venom of Naja naja , was isolated and added to whole human serum it converted and inactivated C3, and the effect on C3 was found to be dependent upon a non-complement plasma protein and on bivalent cations.
Abstract: Cobra factor, a protein of the venom of Naja naja , was isolated. It was characterized as a glycoprotein with a molecular weight of 144,000 and an electrophoretic mobility of a β globulin at pH 8.6. Added to whole human serum it converted and inactivated C3. The effect on C3 was found to be dependent upon a non-complement plasma protein and on bivalent cations. To generate C3-directed enzymatic activity, cobra factor had to enter into a firm complex with the plasma protein, a 5S thermolabile β pseudoglobulin.
TL;DR: This study unravels disturbing deficiencies in dose efficacy and neutralisation capabilities of the currently marketed Indian antivenoms, and emphasises the pressing need to develop region-specific snakebite therapy for the ‘neglected many’.
Abstract: Background Snakebite in India causes the highest annual rates of death (46,000) and disability (140,000) than any other country. Antivenom is the mainstay treatment of snakebite, whose manufacturing protocols, in essence, have remained unchanged for over a century. In India, a polyvalent antivenom is produced for the treatment of envenomations from the so called ‘big four’ snakes: the spectacled cobra (Naja naja), common krait (Bungarus caeruleus), Russell’s viper (Daboia russelii), and saw-scaled viper (Echis carinatus). In addition to the ‘big four’, India is abode to many other species of venomous snakes that have the potential to inflict severe clinical or, even, lethal envenomations in their human bite victims. Unfortunately, specific antivenoms are not produced against these species and, instead, the ‘big four’ antivenom is routinely used for the treatment. Methods We characterized the venom compositions, biochemical and pharmacological activities and toxicity profiles (mouse model) of the major neglected yet medically important Indian snakes (E. c. sochureki, B. sindanus, B. fasciatus, and two populations of N. kaouthia) and their closest ‘big four’ congeners. By performing WHO recommended in vitro and in vivo preclinical assays, we evaluated the efficiencies of the commercially marketed Indian antivenoms in recognizing venoms and neutralizing envenomations by these neglected species. Findings As a consequence of dissimilar ecologies and diet, the medically important snakes investigated exhibited dramatic inter- and intraspecific differences in their venom profiles. Currently marketed antivenoms were found to exhibit poor dose efficacy and venom recognition potential against the ‘neglected many’. Premium Serums antivenom failed to neutralise bites from many of the neglected species and one of the ‘big four’ snakes (North Indian population of B. caeruleus). Conclusions This study unravels disturbing deficiencies in dose efficacy and neutralisation capabilities of the currently marketed Indian antivenoms, and emphasises the pressing need to develop region-specific snakebite therapy for the ‘neglected many’.
TL;DR: Observations confirm the importance of neurotoxic symptoms following bites by krait and cobra species but also suggest a contributory role of generalized rhabdomyolysis in krait victims and emphasize the problem of severe local tissue necrosis in cobra victims.
Abstract: In Anuradhapura, Sri Lanka, 5 patients proved to have been bitten by common kraits (Bungarus caeruelus) and 2 by Sri Lankan cobras (Naja naja naja) were investigated. In all the cases of krait bite the patients were bitten while they were asleep: local signs were negligible but 4 developed symptoms of systemic envenoming including paralysis, muscle pain and tenderness and abdominal pain. Mild myoglobinaemia was found in one case. Of the 2 patients bitten by cobras, one developed severe local swelling which progressed to necrosis and the other local swelling and respiratory paralysis. Response to polyspecific antivenom (Haffkine, India) was neither rapid nor convincing. Venom antigenaemia became undetectable within 2 h of the start of antivenom treatment, but recurred 25 and 65 h later in 2 cases. Among a group of 27 patients treated with this antivenom (including 21 bitten by Russell's vipers), the incidence of early anaphylactic and pyrogenic reactions was high at 52% and 65% respectively. Anticholinesterase did not improve paralysis in 2 patients bitten by kraits. The respiratory failure in 2 patients was successfully treated by mechanical ventilation for 8 and 30 h. These observations confirm the importance of neurotoxic symptoms following bites by these species but also suggest a contributory role of generalized rhabdomyolysis in krait victims and emphasize the problem of severe local tissue necrosis in cobra victims. There is a need for safer and more potent antivenoms for use in Sri Lanka.
TL;DR: Indian cobra venom obtained from three different geographical regions was studied in terms of electrophoretic pattern, biochemical and pharmacological activities and SDS-PAGE banding pattern revealed significant variation in the protein constituents of the three regional venoms.
Abstract: Indian cobra (Naja naja naja) venom obtained from three different geographical regions was studied in terms of electrophoretic pattern, biochemical and pharmacological activities. SDS-PAGE banding pattern revealed significant variation in the protein constituents of the three regional venoms. The eastern venom showed highest indirect hemolysis and hyaluronidase activity. In contrast, western and southern venoms were rich in proteolytic activity. All the three regional venoms were devoid of p-tosyl-L-arginine methyl ester hydrolysing activity. The eastern venom was found to be most lethal among the three regional venoms. The lethal potency varied as eastern > western > southern regional venoms. In addition, all the three regional venoms showed marked variations in their ability to induce symptoms/signs of neurotoxicity, myotoxicity, edema and effect on plasma coagulation process. Polyclonal antiserum prepared against the venom of eastern region cross-reacted with both southern and western regional venoms, but varied in the extent of cross-reactivity by ouchterlony immunodiffusion and ELISA.