Exploring the venom of the forest cobra snake: Toxicovenomics and antivenom profiling of Naja melanoleuca
artículo original
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2017-01-06Autor
Lauridsen, Line Præst
Laustsen, Andreas Hougaard
Lomonte, Bruno
Gutiérrez, José María
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A toxicovenomic analysis of the venomof the forest cobra, N. melanoleuca,was performed, revealing the presence
of a total of 52 proteins by proteomics analysis. The most abundant proteins belong to the three-finger toxins
(3FTx) (57.1 wt%), which includes post-synaptically acting α-neurotoxins. Phospholipases A2 (PLA2) were the
second most abundant group of proteins (12.9 wt%), followed by metalloproteinases (SVMPs) (9.7 wt%), cysteine-
rich secretory proteins (CRISPs) (7.6wt%), and Kunitz-type serine proteinase inhibitors (3.8 wt%). A number
of additional protein families comprised each b3 wt% of venom proteins. A toxicity screening of the fractions,
using the mouse lethality test, identified toxicity in RP-HPLC peaks 3, 4, 5 and 8, all of them containing α-neurotoxins
of the 3FTx family, whereas the rest of the fractions did not show toxicity at a dose of 0.53 mg/kg. Three
polyspecific antivenoms manufactured in South Africa and India were tested for their immunoreactivity against
crude venomand fractions of N.melanoleuca. Overall, antivenoms immunorecognized all fractions in the venom,
the South African antivenom showing a higher titer against the neurotoxin-containing fractions. This
toxicovenomic study identified the 3FTx group of α-neurotoxins in the venom of N. melanoleuca as the relevant
targets to be neutralized.
Biological significance: A toxicovenomic analysis of the venomof the forest cobra, also known as black cobra, Naja
melanoleuca, was performed. Envenomings by this elapid species are characterized by a progressive descending
paralysiswhich starts with palpebral ptosis and, in severe cases, ends up with respiratory arrest and death. A total
of 52 different proteins were identified in this venom. The most abundant protein family was the three-finger
toxin (3FTx) family, which comprises almost 57.1 wt% of the venom, followed by phospholipases A2 (PLA2)
(12.9 wt%). In addition, several other protein families were identified in a much lower percentage in the
venom. A toxicity screening of the fractions, using the mouse lethality assay, identified four peaks as those having
toxicity higher than that of the crude venom. These fractions predominantly contain α-neurotoxins of the 3FTx
family. This toxicovenomic characterization agrees with the clinical and experimental manifestations of
envenomings by this species, in which a strong neurotoxic effect predominates. Therefore, our findings suggest
that immunotherapy against envenomings by N. melanoleuca should be directed towards the neutralization of
3FTxs; this has implications for the improvement of current antivenoms and for the development of novel
antivenoms based on biotechnological approaches. A screening of the immunoreactivity of three antivenoms
being distributed in sub-Saharan Africa revealed that they immunoreact with the fractions containing α-neurotoxins,
although with different antibody titers.
External link to the item
10.1016/j.jprot.2016.08.024Colecciones
- Microbiología [1171]