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.