A Neurotoxic Snake Venom without Phospholipase A2: Proteomics and Cross-Neutralization of the Venom from Senegalese Cobra, Naja senegalensis (Subgenus: Uraeus).

Kin Ying Wong,Kae Yi Tan,Nget Hong Tan,Choo Hock Tan

doi:10.3390/toxins13010060

Abstract

The Senegalese cobra, Naja senegalensis, is a non-spitting cobra species newly erected from the Naja haje complex. Naja senegalensis causes neurotoxic envenomation in Western Africa but its venom properties remain underexplored. Applying a protein decomplexation proteomic approach, this study unveiled the unique complexity of the venom composition. Three-finger toxins constituted the major component, accounting for 75.91% of total venom proteins. Of these, cardiotoxin/cytotoxin (~53%) and alpha-neurotoxins (~23%) predominated in the venom proteome. Phospholipase A2, however, was not present in the venom, suggesting a unique snake venom phenotype found in this species. The venom, despite the absence of PLA2, is highly lethal with an intravenous LD50 of 0.39 µg/g in mice, consistent with the high abundance of alpha-neurotoxins (predominating long neurotoxins) in the venom. The hetero-specific VINS African Polyvalent Antivenom (VAPAV) was immunoreactive to the venom, implying conserved protein antigenicity in the venoms of N. senegalensis and N. haje. Furthermore, VAPAV was able to cross-neutralize the lethal effect of N. senegalensis venom but the potency was limited (0.59 mg venom completely neutralized per mL antivenom, or ~82 LD50 per ml of antivenom). The efficacy of antivenom should be further improved to optimize the treatment of cobra bite envenomation in Africa.

Highlights

Each year, snakebite envenomation causes a death toll that surpasses 100,000, and approximately three times as many permanent disabilities and psychological complications in those survived [1]
The findings provided insights into the pathophysiology and management of N. senegalensis envenomation in Western Africa
Antivenom remains the mainstream and the most realistic treatment of cobra bites, though there is a need to optimize its supply and distribution as well as judicious clinical use in terms of product selection, dosing, and administration. This is the first report on the quantitative venom proteomics of N. senegalensis, a distinct non-spitting cobra species with medical importance in Western Africa

Summary

Introduction

Snakebite envenomation causes a death toll that surpasses 100,000, and approximately three times as many permanent disabilities and psychological complications in those survived [1]. Most of the victims are from impoverished and remote populations, typically those engaging in agricultural activities [2]. The exact morbidity and mortality of snakebite envenomation are, greatly underestimated due to the scarcity of reliable epidemiological data worldwide, in particular rural areas where health systems are suboptimal, and people have limited access to proper treatment. In 2017 snakebite envenomation was reinstated as a priority neglected tropical disease by the. World Health Organization [3]. To solve this long persistent global health crisis, key strategies were proposed to combat the various challenges faced [4].

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Results

Conclusion