Poster Presentation 11th Asia-Pacific Congress of the International Society on Toxinology 2021

Back in black: The differential ability of two enzyme inhibitors in neutralising the anticoagulant effect on plasma by Pseudechis species (Black Snakes) venom. (#123)

Jiaojiao Liu 1 , Abhinandan Chowdhury 1 , Matt Lewin 2 3 , Bryan G Fry 1
  1. Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, Queensland, Australia
  2. California Academy of Sciences, San Francisco, CA, USA
  3. Ophirex, Inc, Corte Madera, CA, USA

 

Black snake (Pseudechis species) venoms have a concentration-dependent anticoagulation potency on human plasma. Envenomation requires antivenom treatment. However, due to the cost and logistic reason such as the lack of cold chain transport, antivenom is not always available when envenomation occurs. Therefore, we investigated the enzyme inhibitors varespladib and prinomastat as temperature-stable, field-deployable first-aid options. We ascertained their ability to neutralise the PLA2-driven anticoagulant activity of P. australis, P. butleri, P. colletti, P. guttatus, P. papuanus, P. rossignolii, and P. sp (NT). Varespladib had a strong inhibitory effect on all seven venoms. However, while prinomastat was effective against P. australis, P. butleri, P. guttatus, P. papuanus, and P. rossignolii it failed to neutralise the P. colletti and P. rossignolii. These results suggest that varespladib binds to a highly conserved site on the toxin surface while in contrast prinomastat binds to a site that is more variable. This suggests that varespladib is a better lead candidate than prinomastat for the remote stabilisation of patients envenomated by Pseudechis species.