The intricate combination of organic and inorganic compounds found in snake venom includes proteins, peptides, lipids, carbohydrates, nucleotides, and metal ions. These components work together to immobilise and consume prey through processes such as paralysis and hypotension. Proteins, both enzymatic and non-enzymatic, form the primary components of the venom. Based on the effects they produce, venom can be classified as neurotoxic, hemotoxic, and cytotoxic. Studies have shown that, after envenomation, proteins in snake venom also contribute significantly to the induction of inflammatory responses which can either have systemic or localized consequences. This review delves into the mechanisms by which snake venom proteins trigger inflammatory responses, focusing on key families such as phospholipase A₂, metalloproteinases, serine proteases, C-type lectins, cysteine-rich secretory proteins, and L-amino acid oxidase. In addition, the role of venom proteins in activating various inflammatory pathways, including the complement system, inflammasomes, and sterile inflammation are also summarized. The available therapeutic options are examined, with a focus on antivenom therapy and its side effects. In general, this review offers a comprehensive understanding of the inflammatory mechanisms that are triggered by snake venom proteins and the side effects of antivenom treatment. All these emphasize the need for effective strategies to mitigate these detrimental effects.

Snakebite envenoming is a neglected tropical disease contributing to a significant number of morbidities and mortalities globally. Reports indicate that venom variation influences antivenom efficacy, which might affect treatment outcomes. The venom composition of Daboia russelii (Russell’s viper), one of the big four snakes in India, has been extensively studied from different geographical regions of India. Nonetheless, the Russell’s viper venom proteome from Kerala (Western Ghats region), together with its study in comparison with the same species’ venom from Tamil Nadu, has not been explored yet. In the current study, Daboia russelii venom from Irula (RVi) and the Western Ghats region in Kerala (RVwg) was characterized through mass spectrometry-based proteomics and few functional assays. The proteomics study identified 52 proteins from 14 snake protein families in RVi and 61 proteins from 17 snake venom protein families in RVwg. Some of the protein families, including DNase and hyaluronidase, as well as vascular endothelial growth factor, were exclusively identified in RVwg venom. Comparative functional analysis indicated that RVwg exhibited higher fibrinogenolytic and hyaluronidase activities, while RVi venom showed higher phospholipase A₂ and L-amino acid oxidase activities. Through ELISA, RVi venom showed an end-point titration value of 1:24,300 for all the antivenoms used in this study, whereas for RVwg, compared to PSAV (Premium serums and vaccines) (1:2700), Virchow and VINS (both 1:8100) antivenoms showed better immunological cross-reactivity. Immunoblotting experiments indicated differential binding and recognition of antigenic epitopes present in both venoms by the polyvalent antivenoms used in the current study. All these findings highlight that the venom proteome varies according to the geographical location, and this significantly influences antivenom efficacy.