The Philippine cobra, Naja philippinensis, is a WHO Category 1 venomous snake of medical importance responsible for fatal envenomation in the northern Philippines. To elucidate the
venom proteome and pathophysiology of envenomation, N. philippinensis
venom proteins were decomplexed with reverse-phase high-performance liquid chromatography, and
protein fractions were subsequently digested with
trypsin, followed by nano-liquid chromatography-tandem mass spectrometry analysis and data mining.
Three-finger toxins (3FTX, 66.64% of total
venom proteins) and
phospholipases A2 (PLA2, 22.88%) constitute the main bulk of
venom proteome. Other
proteins are present at low abundances (<4% each); these include
metalloproteinase,
serine protease,
cobra venom factor,
cysteine-rich secretory
protein, vespryn,
phosphodiesterase, 5'
nucleotidase and
nerve growth factor. In the
three-finger toxin family, the
alpha-neurotoxins comprise solely short
neurotoxins (SNTX, 44.55%), supporting that SNTX is the principal toxin responsible for neuromuscular
paralysis and lethality reported in clinical envenomation.
Cytotoxins (CTX) are the second most abundant 3FTX
proteins in the
venom (21.31%). The presence of CTX correlates with the
venom cytotoxic effect, which is more prominent in murine cells than in human cells. From the practical standpoint, SNTX-driven neuromuscular
paralysis is significant in N. philippinensis envenomation.
Antivenom production and treatment should be tailored accordingly to ensure effective neutralization of SNTX. BIOLOGICAL SIGNIFICANCE: The
venom proteome of Naja philippinensis, the Philippine cobra, is unravelled for the first time. Approximately half the
protein bulk of the
venom is made up of short
neurotoxins (44.55% of the total
venom proteins). As the only
alpha-neurotoxins present in the
venom, short
neurotoxins are the causative toxins of the post-synaptic blockade and fast-onset neuromuscular
paralysis in N. philippinensis envenomation. A substantial amount of
cytotoxins (21.31%) was also detected in N. philippinensis
venom, supporting that the
venom can be cytotoxic although the effect is much weaker in human cells compared to murine cells. The finding is consistent with the low incidence of local tissue
necrosis in N. philippinensis envenomation, although this does not negate the need for monitoring and care of
bite wound in the patients.