Journal
TOXINS
Volume 10, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/toxins10100380
Keywords
snakebite; envenoming; neglected tropical disease; field antidote; inhibitor; taipan; PLA2; phospholipase A2; neurotoxicity; antivenom
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Funding
- Ophirex, Inc.
- Vicerrectoria de Investigacion (Universidad de Costa Rica)
- Doherty Biomedical Postdoctoral Fellowship from the Australian National Health and Medical Research Council
- [W81XWH-17-C-0069]
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There is an unmet need for economical snakebite therapies with long shelf lives that are effective even with delays in treatment. The orally bioavailable, heat-stable, secretory phospholipase A(2) (sPLA(2)) inhibitor, LY333013, demonstrates antidotal characteristics for severe snakebite envenoming in both field and hospital use. A murine model of lethal envenoming by a Papuan taipan (Oxyuranus scutellatus) demonstrates that LY333013, even with delayed oral administration, improves the chances of survival. Furthermore, LY333013 improves the performance of antivenom even after it no longer reverses neurotoxic signs. Our study is the first demonstration that neurotoxicity from presynaptic venom sPLA(2S) can be treated successfully, even after the window of therapeutic antivenom has closed. These results suggest that sPLA(2) inhibitors have the potential to reduce death and disability and should be considered for the initial and adjunct treatment of snakebite envenoming. The scope and capacity of the sPLA2 inhibitors ability to achieve these endpoints requires further investigation and development efforts.
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