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

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.

Preclinical Immuno-recognition and Neutralization of Lethality Assessment of a New Polyvalent Antivenom, VINS Snake Venom Antiserum – African IHS®, against Envenomation of Ten African Viperid and Elapid Snakes

“…[74], whereas information on the preclinical efficacy of some antivenoms against panel of medically significant African snake venoms is limited [7,75]. This current study assessed the preclinical neutralization efficacy of the polyvalent VINS Snake Venom Antiserum -African IHS (SVA-AIHS) against medically relevant snake venoms from Elapidae (Naja spp.…”

“…Previous preclinical studies using VINS venom antiserum exhibited variations and inconsistency in neutralization capacity of the venom antiserum. This may be due to the differences in the source of venom used in the experiment, or with experimental protocol employed, especially, regarding the multiples of LD 50 used as a 'challenge dose' in the lethality experiments [75,79,80]. This assertion was supported by varying reports on the effectiveness of snake venom neutralization potency of VINS venom antiserum products as follows:Wong et al [75] study showed that VINS African Polyvalent Antivenom (VAPAV) was able to cross-neutralize the lethal effect of N. senegalensis (Senegalese cobra) which is a homologue of N. haje (Egyptian cobra).…”

“…This may be due to the differences in the source of venom used in the experiment, or with experimental protocol employed, especially, regarding the multiples of LD 50 used as a 'challenge dose' in the lethality experiments [75,79,80]. This assertion was supported by varying reports on the effectiveness of snake venom neutralization potency of VINS venom antiserum products as follows:Wong et al [75] study showed that VINS African Polyvalent Antivenom (VAPAV) was able to cross-neutralize the lethal effect of N. senegalensis (Senegalese cobra) which is a homologue of N. haje (Egyptian cobra). In our current study, the effectiveness of the SVA-AIHS against the Viperidae and Elapidae snake species venoms supports the hypothesis that immunizing horses with a mixture of the Viperidae and Elapidaevenoms generates antibodies capable of recognizing the majority of components of medically relevant homologous and heterologous viperid and elapid venoms of the genera Bitis, Echis, Dendroaspis andNaja from sub-Saharan Africa.…”

Elucidating the Venom Diversity in Sri Lankan Spectacled Cobra (Naja naja) through De Novo Venom Gland Transcriptomics, Venom Proteomics and Toxicity Neutralization

“…For antivenom neutralization, the study was conducted as previously described in [ 125 ]. In brief, a challenge dose of venom at 2.5 times LD 50 dissolving in saline water was pre-incubated with various dilutions of antivenom (4 dilutions of antivenom tested, 15 μL, 35 μL, 75 μL and 100 μL) at 37 °C for 30 min.…”

What's in a mass?

“…This cast of molecules expands the possibilities of applying mass profiling to study important snake species whose venoms lack PLA 2 s, e.g. the African non-spitting cobras Naja annulifera [22], N. senegalensis [23], N. haje [24] and N. nivea [24].…”