Anticoagulant Micrurus venoms: Targets and neutralization
| Autor: | Christina N. Zdenek, Nicholas J. Youngman, Edgar Neri-Castro, Nathaniel Frank, Melisa Bénard-Valle, José Antonio Portes-Junior, Daniel Dashevsky, Alejandro Alagón, Bryan G. Fry |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Indoles Whole Blood Coagulation Time food.ingredient Phospholipase A2 Inhibitors Antivenom Snake Bites Venom Coral Snakes Acetates Biology Pharmacology Toxicology complex mixtures Neutralization Thromboplastin Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine food Species Specificity Prothrombinase medicine Animals Humans Micrurus Blood Coagulation Coral snake Elapid Venoms Receptors Phospholipase A2 Anticoagulants Tropical disease General Medicine biology.organism_classification medicine.disease Keto Acids 030104 developmental biology chemistry Varespladib 030217 neurology & neurosurgery |
| Zdroj: | Toxicology Letters. 337:91-97 |
| ISSN: | 0378-4274 |
| DOI: | 10.1016/j.toxlet.2020.11.010 |
| Popis: | Snakebite is a neglected tropical disease with a massive global burden of injury and death. The best current treatments, antivenoms, are plagued by a number of logistical issues that limit supply and access in remote or poor regions. We explore the anticoagulant properties of venoms from the genus Micrurus (coral snakes), which have been largely unstudied, as well as the effectiveness of antivenom and a small-molecule phospholipase inhibitor-varespladib-at counteracting these effects. Our in vitro results suggest that these venoms likely interfere with the formation or function of the prothrombinase complex. We find that the anticoagulant potency varies widely across the genus and is especially pronounced in M. laticollaris. This variation does not appear to correspond to previously described patterns regarding the relative expression of the three-finger toxin and phospholipase A2 (PLA2) toxin families within the venoms of this genus. The coral snake antivenom Coralmyn, is largely unable to ameliorate these effects except for M. ibiboboca. Varespladib on the other hand completely abolished the anticoagulant activity of every venom. This is consistent with the growing body of results showing that varespladib may be an effective treatment for a wide range of toxicity caused by PLA2 toxins from many different snake species. Varespladib is a particularly attractive candidate to help alleviate the burden of snakebite because it is an approved drug that possesses several logistical advantages over antivenom including temperature stability and oral availability. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect