{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:24:00Z","timestamp":1791804240609,"version":"4.3.4"},"reference-count":66,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Field Antidote to Snakebite","award":["W81XWH-17-C-0069-ADD"],"award-info":[{"award-number":["W81XWH-17-C-0069-ADD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Antivenom is currently the standard-of-care treatment for snakebite envenoming, but its efficacy is limited by treatment delays, availability, and in many cases, species specificity. Many of the rapidly lethal effects of envenoming are caused by venom-derived toxins, such as phospholipase A2 (sPLA2); therefore, small molecule direct toxin inhibitors targeting these toxins may have utility as initial and adjunct therapies after envenoming. Varespladib (intravenous, IV) and varespladib-methyl (oral) have been shown to potently inhibit sPLA2s from snake venoms in murine and porcine models, thus supporting their further study as potential treatments for snakebite envenoming. In this pilot study, we tested the ability of these compounds to reverse neurotoxic effects of venom from the Australian and Papuan taipan (Oxyuranus scutellatus) subspecies in juvenile pigs (Sus domesticus). The mean survival time for control animals receiving Australian taipan venom (0.03 mg\/kg, n = 3) was 331 min \u00b1 15 min; for those receiving Papuan taipan venom (0.15 mg\/kg, n = 3) it was 178 \u00b1 31 min. Thirteen pigs received Australian taipan venom and treatment with either IV or oral varespladib (or with IV to oral transition) and all 13 survived the duration of the study (\u226596 h). Eight pigs received Papuan taipan venom followed by treatment: Briefly: Two animals received antivenom immediately and survived to the end of the study. Two animals received antivenom treatment delayed 45 min from envenoming and died within 4 h. Two animals received similarly delayed antivenom treatment and were rescued by varespladib. Two animals were treated with varespladib alone after a 45-min delay. Treatment with varespladib only was effective but required repeat dosing over the course of the study. Findings highlight both the importance of early treatment and, as well, a half-life for the investigational inhibitors now in Phase II clinical trials for snakebite. Varespladib rapidly reversed weakness even when administered many hours post-envenoming and, overall, our results suggest that varespladib and varespladib-methyl could be efficacious tools in the treatment of sPLA2-induced weakness from Oxyuranus envenoming. Further clinical study as initial therapy and as potential method of rescue from some types of antivenom-resistant envenomings are supported by these data.<\/jats:p>","DOI":"10.3390\/toxins15090557","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T10:09:50Z","timestamp":1694081390000},"page":"557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Oral and IV Varespladib Rescue Experiments in Juvenile Pigs with Weakness Induced by Australian and Papuan Oxyuranus scutellatus Venoms"],"prefix":"10.3390","volume":"15","author":[{"given":"Lyndi L.","family":"Gilliam","sequence":"first","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Gilliam","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Samuel","sequence":"additional","affiliation":[{"name":"Division of Research Ophirex, Inc., Corte Madera, CA 94925, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5977-7338","authenticated-orcid":false,"given":"Rebecca W.","family":"Carter","sequence":"additional","affiliation":[{"name":"Division of Research Ophirex, Inc., Corte Madera, CA 94925, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Ritchey","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Bulfone","sequence":"additional","affiliation":[{"name":"Center for Exploration and Travel Health, California Academy of Sciences, San Francisco, CA 94118, USA"},{"name":"School of Medicine, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-3081","authenticated-orcid":false,"given":"Jos\u00e9 Mar\u00eda","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Instituto Clodomiro Picado, Facultad de Microbiolog\u00eda, Universidad de Costa Rica, San Jos\u00e9 11501-2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Williams","sequence":"additional","affiliation":[{"name":"Regulation and Prequalification Department (RPQ) at the World Health Organization (WHO), 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela M.","family":"Durkin","sequence":"additional","affiliation":[{"name":"Center for Exploration and Travel Health, California Academy of Sciences, San Francisco, CA 94118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally I.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Division of Research Ophirex, Inc., Corte Madera, CA 94925, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4480-9891","authenticated-orcid":false,"given":"Matthew R.","family":"Lewin","sequence":"additional","affiliation":[{"name":"Division of Research Ophirex, Inc., Corte Madera, CA 94925, USA"},{"name":"Center for Exploration and Travel Health, California Academy of Sciences, San Francisco, CA 94118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0140-6736(18)31224-8","article-title":"Vulnerability to snakebite envenoming: A global mapping of hotspots","volume":"392","author":"Longbottom","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dandona, R., Kumar, G.A., Kharyal, A., George, S., Akbar, M., and Dandona, L. 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