Dermonecrosis caused by a spitting cobra snakebite results from toxin potentiation and is prevented by the repurposed drug varespladib
সংরক্ষণ করুন:
| লেখক: | , , , , , , , , , , , , , |
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| বিন্যাস: | artículo original |
| প্রকাশনার তারিখ: | 2024 |
| বিবরন: | Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The venom of African spitting cobras often causes permanent injury via tissue-destructive dermonecrosis at the bite site, which is ineffectively treated by current antivenoms. To address this therapeutic gap, we identified the aetiological venom toxins responsible for causing local dermonecrosis. While cytotoxic three-finger toxins were primarily responsible for causing spitting cobra cytotoxicity in cultured keratinocytes, their potentiation by phospholipases A2 toxins was essential to cause dermonecrosis in vivo. This evidence of probable toxin synergism suggests that a single toxin-family inhibiting drug could prevent local envenoming. We show that local injection with the repurposed phospholipase A2-inhibiting drug varespladib significantly prevents local tissue damage caused by several spitting cobra venoms in murine models of envenoming. Our findings therefore provide a new therapeutic strategy to more effectively prevent life-changing morbidity caused by snakebite in rural Africa. |
| দেশ: | Kérwá |
| প্রতিষ্ঠান: | Universidad de Costa Rica |
| Repositorio: | Kérwá |
| ভাষা: | Inglés |
| OAI Identifier: | oai:kerwa.ucr.ac.cr:10669/104205 |
| অনলাইন ব্যবহার করুন: | https://hdl.handle.net/10669/104205 https://doi.org/10.1073/pnas.2315597121 |
| মুখ্য শব্দ: | venoms toxins snakebite envenoming neglected tropical diseases drug repurposing |