{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bartlett KE"],"funding":["Medical Research Council","Royal Society","Wellcome Trust","UKRI | Medical Research Council"],"pagination":["e2315597121"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11087757"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["121(19)"],"pubmed_abstract":["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 etiological venom toxins in <i>Naja nigricollis</i> venom 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 A<sub>2</sub> 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."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Dermonecrosis caused by a spitting cobra snakebite results from toxin potentiation and is prevented by the repurposed drug varespladib."],"pmcid":["PMC11087757"],"funding_grant_id":["MR/S00016X/1 and MR/L01839X/1","NIF\\R1\\192161","221712/Z/20/Z","200517/Z/16/Z","MC_PC_15040","221708/Z/20/Z","221712/Z/20/Z and 221708/Z/20/Z"],"pubmed_authors":["Jenkins TP","Albulescu LO","Casewell NR","Laprade W","Hall SR","Wilkinson MC","Harrison RA","Crittenden E","Dawson CA","Saviola AJ","Rasmussen SA","Gutierrez JM","Bartlett KE","Modahl CM"],"additional_accession":[]},"is_claimable":false,"name":"Dermonecrosis caused by a spitting cobra snakebite results from toxin potentiation and is prevented by the repurposed drug varespladib.","description":"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 etiological venom toxins in <i>Naja nigricollis</i> venom 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 A<sub>2</sub> 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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-01T20:22:21.403Z","creation":"2026-05-22T03:08:31.872Z"},"accession":"S-EPMC11087757","cross_references":{"pubmed":["38687786"],"doi":["10.1073/pnas.2315597121"]}}