Abstract
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.
Highlights
Worldwide, it is estimated that 1.8–2.7 million cases of snakebite envenomation occur each year, with fatalities ranging from around 81,000 to 138,000, and around three times as many continue to suffer permanent complications resulting from amputations, deformity and chronic organ failures [1]
To elucidate the toxin gene diversity of the Sri Lankan Spectacled Cobra (N. naja), this study investigated the de novo venom-gland transcriptome of the snake applying nextgeneration sequencing techniques, and the venom proteomics of the snake was studied through a protein decomplexation strategy [32]
De novo sequencing on Illumina platforms generated 54,477,234 paired-end raw reads from the venom gland tissue of the Sri Lankan Naja naja (NN-SL)
Summary
It is estimated that 1.8–2.7 million cases of snakebite envenomation occur each year, with fatalities ranging from around 81,000 to 138,000, and around three times as many continue to suffer permanent complications resulting from amputations, deformity and chronic organ failures [1]. Snakebite envenomation is an important cause of morbidity and mortality that heavily affects impoverished populations in South Asia and Southeast Asia, where the highest incidence of venomous snakebites in the world has been reported [2,3]. In South Asia, the major venomous snake species responsible for causing snakebite envenomation are typically referred to as the “Big Four”, which include the spectacled cobra (Naja naja), common krait (Bungarus caeruleus), Russell’s viper (Daboia russelii) and saw-scaled viper (Echis carinatus). South Asia, greatly influence the biogeographical distribution of the snakes and their adaptation to different habitats. This would have modulated the venom phenotype in terms of toxin composition, contributing to intra-species variation in the snake venom [6–11]. Sri Lanka, which is a tropical island country in the Indian Ocean, is long separated by the Palk Strait and biogeographically distinct from the Indian Peninsula
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