Qualitative Profiling of Venom Toxins in the Venoms of Several <i>Bothrops</i> Species Using High-Throughput Venomics and Coagulation Bioassaying

oleh: Dimoetsha J. C. Weekers, Luis L. Alonso, Anniek X. Verstegen, Julien Slagboom, Jeroen Kool

Format: Article
Diterbitkan: MDPI AG 2024-07-01

Deskripsi

Envenoming resulting from snakebites is recognized as a priority neglected tropical disease by The World Health Organization. The <i>Bothrops</i> genus, consisting of different pitviper species, is considered the most medically significant taxa in Central and South America. Further research into <i>Bothrops</i> venom composition is important to aid in the development of safer and more effective snakebite treatments. In addition, the discovery of <i>Bothrops</i> toxins that could potentially be used for medical or diagnostic purposes is of interest to the pharmaceutical industry. This study aimed to employ high-throughput (HT) venomics to qualitatively analyze venom composition while utilizing coagulation bioassays for identifying coagulopathic toxins and characterizing coagulopathic activity in various <i>Bothrops</i> venoms. Using the recently demonstrated HT venomics workflow in combination with post-column coagulopathic bioassaying, focus was placed at anticoagulant toxins. Well-known procoagulant toxins were also investigated, taking into account that using the HT venomics workflow, procoagulant toxins are especially prone to denaturation during the reversed-phase chromatographic separations performed in the workflow. The findings revealed that the venoms of <i>B. atrox</i> and <i>B. jararaca</i> harbored procoagulant toxins, whereas those of <i>B. alternatus</i> and <i>B. neuwiedi</i> contained both procoagulant and anticoagulant toxins. In general, anticoagulation was associated with phospholipases A<sub>2</sub>s, while procoagulation was associated with snake venom metalloproteinases and snake venom serine proteases. These results showed the identification of coagulopathic venom toxins in the <i>Bothrops</i> venoms analyzed using multiple analytical methods that complement each other. Additionally, each venom underwent qualitative characterization of its composition.