Quantitative proteomics to reveal the composition of Southern India spectacled cobra (Naja naja) venom and its immunological cross-reactivity towards commercial antivenom

Indian cobra (Naja naja) envenomation is frequently reported across Indian subcontinent. Geographical differences in the venom composition of a particular species of snake often leads to inconsistencies in the antivenom neutralization. Consequently, determining the venom proteome from every locale is necessary for the production of effective antivenom. In this study, we deciphered the proteome composition of N. naja venom (NnV) from southern India (SI) by label-free quantitative proteomics that identified 45 proteins (toxins) belonging to 14 venom protein families when searched against Elapidae (taxid: 8602) protein entries in the non-redundant NCBI database. Low molecular mass (<15 kDa) toxins such as PLA2 (18.2%) and 3FTx (37.4%) are the most abundant enzymatic and non-enzymatic proteins, respectively, in SI NnV. Nevertheless, the relative abundance of 3FTxs in SI NnV was found to be lower than the relative abundance of these toxins in previously determined eastern and western India NnV samples. Immuno-recognition and in vitro neutralization of some enzymatic activities and pharmacological properties of SI NnV by commercial polyvalent antivenom evidently demonstrated poor recognition of the most abundant low molecular mass toxins of SI NnV. This finding points to the need for new strategies for antivenom production for the successful treatment of cobra bite.