| Summary: | The Senegalese cobra, <i>Naja senegalensis</i>, is a non-spitting cobra species newly erected from the <i>Naja haje</i> complex. <i>Naja senegalensis</i> 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 A<sub>2</sub>, however, was not present in the venom, suggesting a unique snake venom phenotype found in this species. The venom, despite the absence of PLA<sub>2</sub>, is highly lethal with an intravenous LD<sub>50</sub> 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 <i>N. senegalensis</i> and <i>N. haje</i>. Furthermore, VAPAV was able to cross-neutralize the lethal effect of <i>N. senegalensis</i> venom but the potency was limited (0.59 mg venom completely neutralized per mL antivenom, or ~82 LD<sub>50</sub> per ml of antivenom). The efficacy of antivenom should be further improved to optimize the treatment of cobra bite envenomation in Africa.
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