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

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 (similar to 53%) and alpha-neurotoxins (similar to 23%) predominated in the venom proteome. Phospholipase A(2), however, was not present in the venom, suggesting a unique snake venom phenotype found in this species. The venom, despite the absence of PLA(2), is highly lethal with an intravenous LD50 of 0.39 mu g/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 similar to 82 LD50 per ml of antivenom). The efficacy of antivenom should be further improved to optimize the treatment of cobra bite envenomation in Africa.

Automated summary

The Senegalese cobra, Naja senegalensis, has a venom composition dominated by three-finger toxins, including cardiotoxin/cytotoxin and alpha-neurotoxins. Unlike other cobra species, the venom of N. senegalensis does not contain phospholipase A(2), making it unique. Although highly lethal, the efficacy of existing antivenom in neutralizing the venom's effects is limited, suggesting a need for further improvement in treatment strategies for cobra bite envenomation in Africa.