Ophiophagus hannah Venom: Proteome, Components Bound by Naja kaouthia Antivenin and Neutralization by N. kaouthia Neurotoxin-Specific Human ScFv

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.

Venom-gland transcriptome and venom proteome of the Malaysian king cobra (Ophiophagus hannah)

“…The study verified the presence of some previously isolated toxins but shed little light on the venom proteome. Another recent report on king cobra(s) venom of probable Thai origin profiled the venom as well, detecting 14 protein types/families (including hypothetical proteins), but again without the estimation of relative toxin abundance [ 25 ]. The 1D electrophoretic gel findings of the Thai king cobra venom appeared similar to that reported by Chang et al [ 19 ], suggesting that 3FTxs are the major component of king cobra venoms of different localities.…”

Protein Discovery: Combined Transcriptomic and Proteomic Analyses of Venom from the Endoparasitoid Cotesia chilonis (Hymenoptera: Braconidae)

“…Endonucleases have been reported in the venom of some snakes [74], Physalia physalis (Cnidaria: Siphonophora) [75], Chrysaora quinquecirrha (Cnidaria, Scyphozoa) [76], and Nasonia vitripennis [46]. …”

Locked-in Syndrome Following a King Cobra (Ophiophagus hannah) Envenomation

“…He described the experience as "feeling trapped and totally helpless". (Danpaiboon et al 2014). It consists of at least 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/basic pancreatic trypsin inhibitor (BPTI)-type inhibitors, growth factor activators and others (coagulation factor, endonuclease, 5'-nucleotidase) (Danpaiboon et al 2014;Li et al 1994).…”

“…(Danpaiboon et al 2014). It consists of at least 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/basic pancreatic trypsin inhibitor (BPTI)-type inhibitors, growth factor activators and others (coagulation factor, endonuclease, 5'-nucleotidase) (Danpaiboon et al 2014;Li et al 1994). A functional proteomics study of O. hannah venom sampled from five distinct geographic regions revealed fast evolution and dynamic translational regulation of the venom composition (Chang et al 2013).…”