Proteomics and preclinical antivenom neutralization of the mangrove pit viper (Trimeresurus purpureomaculatus, Malaysia) and white-lipped pit viper (Trimeresurus albolabris, Thailand) venoms

Abstract

• Venom proteomes of MTP and TTA were investigated and compared. • MTP: Malaysian Trimereusurus purpureomaculatus ; TTA: Thai Trimeresurus albolabris . • Metalloproteinases and phospholipases A 2 were the most abundant proteins in the venoms. • Both venoms exhibited comparable procoagulant, hemorrhagic and lethal activities. • Green pit viper antivenom is effective in neutralizing the toxicity of MTP venom. The Malaysian mangrove pit viper ( Trimeresurus purpureomaculatus , MTP) and the Thai white-lipped green pit viper ( Trimeresurus albolabris , TTA) are both WHO medically important venomous snakes. They occupy different geographical habitats and are morphologically varied, hence potential variation in the compositions, activities and antigenicity of the venoms is anticipated. In the treatment of envenomation, a species-specific antivenom is available for T. albolabris but not T. purpureomaculatus . This study therefore investigated and compared the proteomes and toxicity of the two venoms, followed by preclinical evaluation of the immunoreactivity and neutralization efficacy of green pit viper antivenom (GPVAV) against the venoms. Reverse-phase high performance liquid chromatography and nano-ESI-LC-MS/MS identified 14 protein families in both venoms. Snake venom metalloproteinase (SVMP, >30% of total venom proteins) and phospholipase A 2 (PLA 2 , >18%) represent the most abundant protein families, followed by disintegrin, C-type lectin, serine protease and other minor proteins. The toxins correlated well with the potent procoagulant and hemorrhagic activities of the venoms, and both venoms were moderately lethal in mice ( i.v. LD 50 = 0.50−0.89 µg/g). GPVAV produced in Thailand was immunoreactive toward the heterologous MTP venom, and effectively cross-neutralized the procoagulant, hemorrhagic and lethal effects of the venom albeit at a lower potency compared to the neutralization of the homologous TTA venom. The finding supports the paraspecific use of GPVAV as a pharmacotherapy in the treatment of T. purpureomaculatus envenomation.