Snake Venomics and Antivenomics of Cape Cobra (Naja nivea) from South Africa: Insights into Venom Toxicity and Cross-Neutralization Activity

Naja nivea (Cape Cobra) is endemic to southern Africa. Envenoming by N. nivea is neurotoxic, resulting in fatal paralysis. Its venom composition, however, has not been studied in depth, and specific antivenoms against it remain limited in supply. Applying a protein decomplexation approach, this study unveiled the venom proteome of N. nivea from South Africa. The major components in the venom are cytotoxins/cardiotoxins (similar to 75.6% of total venom proteins) and alpha-neurotoxins (similar to 7.4%), which belong to the three-finger toxin family. Intriguingly, phospholipase A(2) (PLA(2)) was undetected-this is a unique venom phenotype increasingly recognized in the African cobras of the Uraeus subgenus. The work further showed that VINS African Polyvalent Antivenom (VAPAV) exhibited cross-reactivity toward the venom and immunorecognized its toxin fractions. In mice, VAPAV was moderately efficacious in cross-neutralizing the venom lethality with a potency of 0.51 mg/mL (amount of venom completely neutralized per milliliter of antivenom). In the challenge-rescue model, VAPAV prevented death in 75% of experimentally envenomed mice, with slow recovery from neurotoxicity up to 24 h. The finding suggests the potential para-specific utility of VAPAV for N. nivea envenoming, although a higher dose or repeated administration of the antivenom may be required to fully reverse the neurotoxic effect of the venom.

Automated summary

This study revealed the composition of the venom of the Cape Cobra Naja nivea, showing that it mainly contains cytotoxins/cardiotoxins and alpha-neurotoxins. The VINS African Polyvalent Antivenom (VAPAV) exhibited cross-reactivity with the venom and showed moderate efficacy in neutralizing the venom lethality in mice. However, a higher dose or repeated administration of the antivenom may be required to fully reverse the neurotoxic effect of the venom.