Venomics, lethality and neutralization of Naja kaouthia (monocled cobra) venoms from three different geographical regions of Southeast Asia.
Previous studies showed that venoms of the monocled cobra, Naja kaouthia from Thailand and Malaysia are substantially different in their median lethal doses. The intraspecific venom variations of N. kaouthia, however, have not been fully elucidated. Here we investigated the venom proteomes of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V) through reverse-phase HPLC, SDS-PAGE and tandem mass spectrometry. The venom proteins comprise 13 toxin families, with three-finger toxins being the most abundant (63-77%) and the most varied (11-18 isoforms) among the three populations. NK-T has the highest content of neurotoxins (50%, predominantly long neurotoxins), followed by NK-V (29%, predominantly weak neurotoxins and some short neurotoxins), while NK-M has the least (18%, some weak neurotoxins but less short and long neurotoxins). On the other hand, cytotoxins constitute the main bulk of toxins in NK-M and NK-V venoms (up to 45% each), but less in NK-T venom (27%). The three venoms show different lethal potencies that generally reflect the proteomic findings. Despite the proteomic variations, the use of Thai monovalent and Neuro polyvalent antivenoms for N. kaouthia envenomation in the three regions is appropriate as the different venoms were neutralized by the antivenoms albeit at different degrees of effectiveness.


CONCLUSIONS
Biogeographical variations were observed in the venom proteome of monocled cobra (Naja kaouthia) from Malaysia, Thailand and Vietnam. The Thai N. kaouthia venom is particularly rich in long neurotoxins, while the Malaysian and Vietnamese specimens were predominated with cytotoxins. The differentially expressed toxin profile accounts for the discrepancy in the lethal dose of the venom from different populations. Commercially available Thai antivenoms (monovalent and polyvalent) were able to neutralize the three venoms at different effective doses, hence supporting their uses in the three regions. While dose adjustment according to geographical region seems possible, changes to standard recommended dosage should only be made if further study validates that the monocled cobras within a population do not exhibit remarkable inter-individual venom variation.
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Kae Yi
KY
Tan
Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; University of Malaya Centre for Proteomics Research (UMPCR), University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: tanchoohock@gmail.com.
Choo Hock
CH
Tan
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; University of Malaya Centre for Proteomics Research (UMPCR), University of Malaya, 50603 Kuala Lumpur, Malaysia.
Shin Yee
SY
Fung
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; University of Malaya Centre for Proteomics Research (UMPCR), University of Malaya, 50603 Kuala Lumpur, Malaysia.
Nget Hong
NH
Tan
D000595:Amino Acid Sequence; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use; D000997:Antivenins / Q000627:therapeutic use*; D001210:Asia, Southeastern; D003039:Cobra Neurotoxin Proteins / Q000737:chemistry* / Q000506:poisoning*; D004546:Elapid Venoms / Q000737:chemistry* / Q000506:poisoning*; D007928:Lethal Dose 50; D008296:Malaysia; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D012909:Snake Bites / Q000139:chemically induced / Q000188:drug therapy*; D015996:Survival Rate; D013785:Thailand; D016896:Treatment Outcome; D014744:Vietnam
D000931:Antidotes; D000997:Antivenins; D003039:Cobra Neurotoxin Proteins; D004546:Elapid Venoms; C521753:Naja kaouthia venom
Antivenom neutralization; Geographical variation; Monocled cobra; Naja kaouthia; Three-finger toxins; Venom proteome