Proteogenomics-guided functional venomics resolves the toxin arsenal and activity of Deinagkistrodon acutus venom

Avella, Ignazio; Schulte, Lennart; Hurka, Sabine; Damm, Maik; Eichberg, Johanna; Schiffmann, Susanne; Henke, Marina; Timm, Thomas; Lochnit, Günther; Hardes, Kornelia; Vilcinskas, Andreas; Lüddecke, Tim

doi:10.1016/j.ijbiomac.2024.135041

International Journal of Biological Macromolecules

2024

DOI: 10.1016/j.ijbiomac.2024.135041

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Proteogenomics-guided functional venomics resolves the toxin arsenal and activity of Deinagkistrodon acutus venom

Ignazio Avella,

Lennart Schulte,

Sabine Hurka

et al.

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Cited by 2 publications

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The Toxin Diversity, Cytotoxicity, and Enzymatic Activity of Cape Cobra (Naja nivea) Venom

Lüddecke,

Avella,

Damm

et al. 2024

Toxins

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“True” cobras (genus Naja) are among the venomous snakes most frequently involved in snakebite accidents in Africa and Asia. The Cape cobra (Naja nivea) is one of the African cobras of highest medical importance, but much remains to be learned about its venom. Here, we used a shotgun proteomics approach to better understand the qualitative composition of N. nivea venom and tested its cytotoxicity and protease activity as well as its effect on intracellular Ca2+ release and NO synthesis. We identified 156 venom components representing 17 protein families, with the dominant ones being three-finger toxins, mostly of the short-chain type. Two-thirds of the three-finger toxin entries identified were assigned as cytotoxins, while the remainder were categorized as neurotoxins, including short-chain, long-chain, and ancestral three-finger toxins. We also identified snake venom metalloproteinases and members of CRISP, l-amino acid oxidase, and other families. Protease activity and its effect on intracellular Ca2+ release and NO synthesis were low. Phospholipase A2 activity was surprisingly high, despite this toxin family being marginally recovered in the analyzed venom. Cytotoxicity was relevant only at higher venom concentrations, with macrophage and neuroblastoma cell lines showing the lowest viability. These results are in line with the predominantly neurotoxic envenomation symptoms caused by Cape cobra bites. The present overview of the qualitatively complex and functionally intriguing venom of N. nivea may provide insights into the pathobiochemistry of this species’ venom.

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The Toxin Diversity, Cytotoxicity, and Enzymatic Activity of Cape Cobra (Naja nivea) Venom

Lüddecke,

Avella,

Damm

et al. 2024

Toxins

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show abstract

Virtual Screening and Mechanism Analysis of Effective Components from Several Chinese Herbs to Inhibit dPLA2 of <i>Deinagkistrodon</i> <i>acutus</i> Venom

Zhang,

Xiao,

Lai

et al. 2024

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Proteogenomics-guided functional venomics resolves the toxin arsenal and activity of Deinagkistrodon acutus venom

Cited by 2 publications

References 81 publications

The Toxin Diversity, Cytotoxicity, and Enzymatic Activity of Cape Cobra (Naja nivea) Venom

The Toxin Diversity, Cytotoxicity, and Enzymatic Activity of Cape Cobra (Naja nivea) Venom

Virtual Screening and Mechanism Analysis of Effective Components from Several Chinese Herbs to Inhibit dPLA2 of <i>Deinagkistrodon</i> <i>acutus</i> Venom

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