Comparative analysis of Naja kaouthia venom from North-East India and Bangladesh and its cross reactivity with Indian polyvalent antivenoms

Deka, Archana; Reza, Abu; Hoque, Kazi Md. Faisal; Deka, Kamalakshi; Saha, Swati; Doley, Robin

doi:10.1016/j.toxicon.2019.03.025

Cited by 23 publications

(32 citation statements)

References 82 publications

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“…For example, with the exception of Premium Serums, one of the bands at 55 kDa was not recognized by any of the antivenoms. Similarly, as reported previously in various medically important Indian snakes [45–47], low molecular weight toxins (~10 kDa) were largely unrecognized. Comparison of these immunoblots to the negative control (naive horse IgG) reveals non-specific binding of IgGs to these largely abundant low molecular weight toxins, especially in Elapidae snakes (Fig 5B).…”

Section: Resultssupporting

confidence: 68%

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Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies

et al. 2019

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BackgroundSnakebite 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.MethodsWe 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.FindingsAs 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).ConclusionsThis 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’.

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Section: Resultssupporting

confidence: 68%

“…Additionally, the population of N . kaouthia from Arunachal Pradesh also exhibited lower toxicity in comparison to the other Northeast Indian and Bangladesh populations investigated previously [45, 94].…”

Section: Discussionmentioning

confidence: 72%

Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies

et al. 2019

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“…2-DE for crude venom of WA, LCA and CN snakes was carried out separately using a modification of a previous study [28] and in accordance with laboratory guidelines. Three hundred micrograms of each venom sample were separately dissolved in 100 μl of rehydration solution containing 8 M urea, 2% (w/v) CHAPS (Co. Sigma), 20 mM DTT (dithiothreitol, Co, Merck, Germany), 0.5% (v/v) immobilized pH gradient (IPG) buffer (Merck), and 0.002% (w/v) bromophenol blue.…”

Section: Two-dimensional Gel Electrophoresis (2-de)mentioning

confidence: 99%

Comparison of venom from wild and long-term captive Gloydius caucasicus and the neutralization capacity of antivenom produced in rabbits immunized with captive venom

Rasoulinasab

Shahbazzadeh

et al. 2020

Heliyon

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Gloydius caucasicus (NIKOLSKY, 1916) is a member of the Viperidae family in Iran. Comprehensive understanding of the toxigenic characteristics of snake venom is important for clinical monitoring of snakebite patients and effective therapy. We compared the toxic activities of venoms and the neutralization capacity of antivenoms produced with venoms from wild adult (WA) with long-term captive adult (LCA) of G. caucasicus in order to obtain more effective antivenom from LCA in therapy, and subsequently protect G. caucasicus from overharvesting for its venom, which poses a real threat of extinction for the species. Our results showed that LD 50 of WA and LCA were 16.8 μg/dose and 17.7 μg/dose, respectively. Lower hemorrhagic and necrotic (p ≥ 0.05), and higher coagulative and edematogenic activities (p ≤ 0.05) were observed in WA compared with LCA venom. Also, captive-born neonates exhibited weaker toxic activities compared with captive adult snakes, which could be an age-related difference. Study data illustrated that effective capacity of LCA antivenom to neutralize the toxic activities of WA viper venom. According to the results, about 0.4–4 μl of LCA antivenom is required to neutralize the toxic activities of 1 μg of WA venom, indicating its efficacy in treatment of snakebites in humans. On this basis, it is recommended that capture of wild snakes for their venom be discontinued to reduce their future extinction risk.

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“…Current -omics technologies allow high throughput sequencing and identification of snake venom proteins and toxin genes, thereby unveiling the diversity of toxin genes and the dynamic range of venom complexities in many species, including widely distributed venomous snakes such as the cobras. Previous enzymatic, proteomic and transcriptomic studies of Naja species have revealed significant inter- and intra-species variation in venom composition and toxin gene diversity [ 6 , 7 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. More recently, the genome of Indian N. naja (Kerala State) was reported, and the venom-gland transcriptomes of six cobra specimens sourced from Kerala in India and Kentucky Reptile Zoo in USA were profiled [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Elucidating the Venom Diversity in Sri Lankan Spectacled Cobra (Naja naja) through De Novo Venom Gland Transcriptomics, Venom Proteomics and Toxicity Neutralization

Wong

Tan

et al. 2021

Toxins

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Inadequate effectiveness of Indian antivenoms in treating envenomation caused by the Spectacled Cobra/Indian Cobra (Naja naja) in Sri Lanka has been attributed to geographical variations in the venom composition. This study investigated the de novo venom-gland transcriptomics and venom proteomics of the Sri Lankan N. naja (NN-SL) to elucidate its toxin gene diversity and venom variability. The neutralization efficacy of a commonly used Indian antivenom product in Sri Lanka was examined against the lethality induced by NN-SL venom in mice. The transcriptomic study revealed high expression of 22 toxin genes families in NN-SL, constituting 46.55% of total transcript abundance. Three-finger toxins (3FTX) were the most diversely and abundantly expressed (87.54% of toxin gene expression), consistent with the dominance of 3FTX in the venom proteome (72.19% of total venom proteins). The 3FTX were predominantly S-type cytotoxins/cardiotoxins (CTX) and α-neurotoxins of long-chain or short-chain subtypes (α-NTX). CTX and α-NTX are implicated in local tissue necrosis and fatal neuromuscular paralysis, respectively, in envenomation caused by NN-SL. Intra-species variations in the toxin gene sequences and expression levels were apparent between NN-SL and other geographical specimens of N. naja, suggesting potential antigenic diversity that impacts antivenom effectiveness. This was demonstrated by limited potency (0.74 mg venom/ml antivenom) of the Indian polyvalent antivenom (VPAV) in neutralizing the NN-SL venom. A pan-regional antivenom with improved efficacy to treat N. naja envenomation is needed.

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Comparative analysis of Naja kaouthia venom from North-East India and Bangladesh and its cross reactivity with Indian polyvalent antivenoms

Cited by 23 publications

References 82 publications

Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies

Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies

Comparison of venom from wild and long-term captive Gloydius caucasicus and the neutralization capacity of antivenom produced in rabbits immunized with captive venom

Elucidating the Venom Diversity in Sri Lankan Spectacled Cobra (Naja naja) through De Novo Venom Gland Transcriptomics, Venom Proteomics and Toxicity Neutralization

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