Year: 2025
Type: article
Abstract: Examination of venom constituent bioactivities from diverse venomous animals shows certain highly conserved classes, including enzymes (e.g., phospholipases and metalloproteinases) and pore-forming proteins. While antivenoms targeting other unique and lethal venom components have proven to be life-saving, venom-enzyme-driven tissue damage and morbidity persists. Broad-acting enzyme inhibitors demonstrate the potential to augment antivenom approaches. In this study, we investigate the potential utility of certain broad-acting inhibitors in cubozoa for the first time. Fluorogenic assays were used to determine the phospholipase A2 (PLA2) and matrix metalloproteinase (MMP) activity of the Hawaiian box jellyfish, Alatina alata, and this was compared to representative elapid, viper, and bee venoms. In vitro, evaluation of selected small-molecule inhibitors demonstrated the ability and feasibility of the broad-acting therapeutic doxycycline, which inhibited the PLA2 and MMP activity of A. alata (approximately 50% reduction at 0.1 mM (95% CI 0.06–0.15) and 2.1 mM (95% CI 1.4–3.0), respectively), in addition to both snake venoms. Additionally, copper gluconate broadly inhibited the PLA2 activity of bee, snake, and jellyfish venoms. While all venoms are complex mixtures of bioactive molecules, these studies demonstrate that targeting common class components with broad-acting inhibitors shows promise in clinical and preclinical management.
Source: Toxins
Institutions: University of Hawaiʻi at Mānoa, University of Birmingham
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,258
Funders: U.S. Department of Defense, Hawaii Community Foundation, Victoria S. and Bradley L. Geist Foundation, National Institutes of Health, United States Special Operations Command, National Institute on Drug Abuse, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Center for Research Resources
Awards: G1535317573, Pacific Center for Emerging Infectious Diseases Research, G1634858739, G1807616862, G2112970142, G2183534212, G3009622552, Bioscience Research Infrastructure Development for Grant Enhancement and Success, G4119534169, G4358376354, G5659760395, G5850682332, G6336628147, G6539707273, G7434784360, G7531311982, G780258685, G8440188047, G8878129276, G9000023334, G9000093750, G9000115593, G9000193642
OpenAlex ID: W4409301178