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

## TL;DR

A natural inhibitor from one snake's blood reduces the harmful effects of venom from another snake, suggesting a new approach to anti-venom treatments.

## Contribution

A recombinant PLA2 inhibitor from Sinonatrix annularis is shown to mitigate the hemorrhagic effects of Daboia siamensis venom.

## Key findings

- D. siamensis venom had the highest PLA2 activity among five tested snake venoms.
- PLIϒ reduced in vitro PLA2 activity by 34.8% and hemorrhagic spots in mice by 30.2%.

## Abstract

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.

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).

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.

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.

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