Recombinant phospholipase A2 inhibitor of Sinonatrix annularis (ringed water snake) attenuates hemorrhagic action of the venom from Daboia siamensis (Siamese Russell’s viper)

Wichit Thaveekarn; Jureeporn Noiphrom; Asada Leelahavanichkul; Orawan Khow

doi:10.2478/abm-2025-0038

Abstract

Background

Phospholipase A₂ (PLA₂) is a common enzyme in snake venoms from many species that hydrolyzes phospholipids in cell membranes, causing local and systemic adverse effects. Interestingly, PLA₂ inhibitors in the snake blood are a natural neutralization against PLA₂ that is leaked into the circulation. Hence, synthesizing liver PLA₂ inhibitors might be a novel and effective anti-venom strategy.

Objective

To test if PLA₂ inhibitor gamma form (PLIϒ) reduces the hemorrhagic effect of crude Daboia siamensis (D. siamensis) (a venomous viper with high PLA₂ abundance in the venom).

Methods

PLIϒ was synthesized and purified from the data of Sinonatrix annularis. Then, PLA₂ activity in the snake venoms was screened and tested against PLA₂ activity from crude D. siamensis venom. The hemorrhage effect of crude D. siamensis was measured with the minimum hemorrhagic activity dose in mice with and without PLIϒ.

Results

D. siamensis had the highest PLA₂ activity among the 5 selected venomous snakes. The PLIϒ reduced the PLA₂ activity of crude D. siamensis by up to 34.8% (in vitro) and decreased hemorrhagic spots in mice by up to 30.2% on the inner surface of mouse skins compared with controls.

Conclusion

PLIϒ reduced PLA₂ activity and was effective in mitigating the hemorrhagic effect of crude D. siamensis.

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