The Venom Proteome and Immunorecognition Profile of Clinically Important Echis carinatus sochureki from Northwestern India Underscores the Need for Regionally Specific Antivenoms

The saw-scaled viper <i>Echis carinatus</i>, one of the "Big Four" causes of snakebites in India, is found from Sri Lanka to eastern Iraq. To investigate clinical reports regarding the limited efficacy of Indian polyvalent antivenom (IPAV) against envenomation in <i>Echis carinatus sochureki</i> (ECS) in northwestern India, we obtained 22 snakes from three locations in Rajasthan and identified 148-174 toxin isoforms belonging to 21-25 toxin families in their venom using a bottom-up proteomics approach. All samples showed a high abundance of snake venom metalloproteinases (SVMPs), particularly SVMP class III. Other major components were phospholipases A₂, L-amino-acid oxidases, snake venom serine proteases and snaclecs (C-type lectins). Variation in venom composition among locations in Rajasthan, compared to <i>E. c. carinatus</i> (ECC) from southern India, was primarily due to differences in the relative abundance of these toxin families. Recognition of all venom components by IPAV was poor at lower antivenom concentrations. Notably, SVMP classes II and III were poorly recognized at all venom-to-antivenom ratios in all ECS venoms, and a plasma clotting assay revealed poor neutralization of procoagulant activity. This collaborative study highlights the need for the development of regional antivenoms to effectively treat snakebites in northwestern India.