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Toxins 2018, 10(10), 380; https://doi.org/10.3390/toxins10100380

Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom

1
Ophirex, Inc., Corte Madera, CA 94925, USA
2
California Academy of Sciences, San Francisco, CA 94118, USA
3
Facultad de Microbiología, Instituto Clodomiro Picado, Universidad de Costa Rica, an José 11501-2060, Costa Rica
4
Queen Elizabeth Hospital, Kings Lynn, Norfolk PE30 4ET, UK
5
Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 94143, USA
6
Department of Pharmacology and Therapeutics, Australian Venom Research Unit, University of Melbourne, Parkville, VIC 3010, Australia
*
Authors to whom correspondence should be addressed.
Received: 5 September 2018 / Revised: 17 September 2018 / Accepted: 17 September 2018 / Published: 20 September 2018
(This article belongs to the Section Animal Venoms)
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Abstract

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 A2 (sPLA2) 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 sPLA2S can be treated successfully, even after the window of therapeutic antivenom has closed. These results suggest that sPLA2 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. View Full-Text
Keywords: snakebite; envenoming; neglected tropical disease; field antidote; inhibitor; taipan; PLA2; phospholipase A2; neurotoxicity; antivenom snakebite; envenoming; neglected tropical disease; field antidote; inhibitor; taipan; PLA2; phospholipase A2; neurotoxicity; antivenom
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Lewin, M.R.; Gutiérrez, J.M.; Samuel, S.P.; Herrera, M.; Bryan-Quirós, W.; Lomonte, B.; Bickler, P.E.; Bulfone, T.C.; Williams, D.J. Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom. Toxins 2018, 10, 380.

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