Abstract
Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah) is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5’-nucleotidase). N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv) cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins.
Highlights
Snake envenomation is an important health problem and occupational hazard among outdoor workers, such as farmers, plantation workers and agricultural harvesters, in tropical and subtropical areas, where venomous snakes have a habitat predilection [1,2,3]
The lyophilized antivenin was dissolved in ten mL of ultrapure sterile distilled water (UDW), while the venom was dissolved in one mL of normal saline solution (NSS)
They could be classified into 14 different protein types/families (Table A1), i.e., three finger toxin, phospholipase, cysteine-rich secretory protein (CRiSP), cobra venom factor/complement C3, muscarinic toxin, L-amino acid oxidase, hypothetical protein, low cysteine protein, phosphodiesterase, protease, Vespryn toxin, Kunitz, growth factor activator and others
Summary
Snake envenomation is an important health problem and occupational hazard among outdoor workers, such as farmers, plantation workers and agricultural harvesters, in tropical and subtropical areas, where venomous snakes have a habitat predilection [1,2,3]. The treatment mainstay of the venomous snakebites in Thailand relies on the horse-derived antivenins produced by. The antivenins may be either monospecific for cases when the causative snakes are known or polyspecific, which neutralizes more than one venom species when biting snakes are not identified [5]. Insight into the venom proteomes of individual venomous snake species that inhabit common geographical areas/localities, like O. hannah and N. kaouthia, which produce similar clinical features [7,8] and the identification of common components shared among their venoms should be useful information for treatment indication when homologous and polyspecific antivenins are not available. The O. hannah venom proteome was characterized, and the components cross-reactive to horse derived-monospecific N. kaouthia antivenin were determined
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