A comparative study of venomics of Naja naja from India and Sri Lanka, clinical manifestations and antivenomics of an Indian polyspecific antivenom

• Comparative venomics of Naja naja from Indian and Sri Lanka have been carried out.
• Differences in venom protein compositions representing intra-specific variations have been documented.
• The neurotoxin/cytotoxin contents of the venoms explained well the clinical symptoms produced by these venoms.
• Antivenomics study of an Indian antivenom showed lower binding affinity against the Sri Lankan cobra venom proteins.
• The lower antibody binding affinity explained the poor efficacy of the Indian antivenom against Sri Lankan cobra envenoming.

Naja naja (Indian cobra) from Sri Lanka and India is the WHO Category 1 medically important snakes in both countries. Some antivenom produced against Indian N. naja (NNi) were less effective against Sri Lankan N. naja (NNsl). Proteomes of NNi and NNsl venoms were studied by RP-HPLC, SDS-PAGE and LC/MS/MS. Six protein families were identified in both venoms with the most abundant were the 3 finger toxins (3FTs) where cytotoxins (CTX) subtype predominated, followed by phospholipase A2, cysteine-rich venom protein, snake venom metalloproteases, venom growth factors, and protease inhibitors. Qualitative and quantitative differences in the venomics profiles were observed. Some proteins were isolated from either NNi or NNsl venom. Postsynaptic neurotoxins (NTX) were identified for the first time in NNsl venom. Thus, there are geographic intra-specific variations of venom composition of the two N. naja. The relative abundance of CTX and NTX explained well the clinical manifestations of these venoms. Antivenomics study of an Indian antivenom (Vins) showed the antibodies effectively bound all venom toxins from both snakes but more avidly to the Indian venom proteins. The lower antibody affinity towards the ‘heterologous’ venom was the likely cause of poor efficacy of the Indian antivenom used to treat NNsl envenoming.

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