Interspecific and Intraspecific Variation in Venom Proteomics, Composition, and Antivenom Efficacy of Thai Cobras (Naja spp.): Highlighting the Distinct Profile of the Newly Identified Naja fuxi

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Interspecific and Intraspecific Variation in Venom Proteomics, Composition, and Antivenom Efficacy of Thai Cobras (Naja spp.): Highlighting the Distinct Profile of the Newly Identified Naja fuxi

Abstract

Cobras (Naja spp.) account for a significant number of snakebite incidents in Thailand. The monocled cobra (Naja kaouthia) has historically been considered the only non-spitting species, but recent evidence indicates population-level diversification in central and southern regions. Additionally, a newly described non-spitting species, the mountain cobra (Naja fuxi), has been identified in mountainous areas. This study investigates venom variation among Thai Naja species and populations and evaluates the efficacy of monovalent and polyvalent Thai antivenoms. Proteomic analyses revealed that three-finger toxins dominate Naja venoms, whereas N. fuxi exhibits a distinct profile enriched in snake venom metalloproteinases and cysteine-rich secretory proteins, suggesting evolutionary divergence. Electrophoretic and enzymatic assays demonstrated species- and population-specific differences in phospholipase A₂, acetylcholinesterase, hyaluronidase, L-amino acid oxidase, phosphodiesterase, and protease activities. Cytotoxicity assays on human fibroblasts and mouse myoblasts showed that N. kaouthia (southern) and N. fuxi venoms caused the most potent and time-dependent cell damage, whereas central N. kaouthia and king cobra (Ophiophagus hannah) venoms were less cytotoxic. Immunoreactivity and neutralisation assays indicated that the species-specific monovalent antivenom effectively binds and neutralises cobra venoms, while neuro-polyvalent antivenom provides moderate cross-protection, and haemato-polyvalent antivenom is highly specific to viperid venom. These findings reveal substantial inter- and intraspecific venom variation in Thai cobras, emphasising the importance of population-level considerations in antivenom design and snakebite management. Continuous evaluation of venom composition and antivenom efficacy is essential to optimise clinical outcomes across Thailand’s diverse landscapes.
Ratnarathorn, N., Panyain, N., Noiphrom, J., Thaveekarn, W., Taewcharoen, N., Khow, O., Chanhome, L., Laoungbua, P., Tawan, T., & Kumkate, S. (2026). Interspecific and Intraspecific Variation in Venom Proteomics, Composition, and Antivenom Efficacy of Thai Cobras (Naja spp.): Highlighting the Distinct Profile of the Newly Identified Naja fuxi. Acta Tropica, 108065. https://doi.org/10.1016/j.actatropica.2026.108065