Animal-derived antivenoms are the only specific therapies currently available for the treatment of snake envenoming, but these products have a number of limitations associated with their efficacy, safety and affordability for use in tropical snakebite victims. Small molecule drugs and drug candidates are regarded as promising alternatives for filling the critical therapeutic gap between snake envenoming and effective treatment. In this study, by using an advanced analytical technique that combines chromatography, mass spectrometry and bioassaying, we investigated the effect of several small molecule inhibitors that target phospholipase A ₂ (varespladib) and snake venom metalloproteinase (marimastat, dimercaprol and DMPS) toxin families on inhibiting the activities of coagulopathic toxins found in Viperinae snake venoms. The venoms of Echis carinatus, Echis ocellatus, Daboia russelii and Bitis arietans , which are known for their potent coagulopathic toxicities, were fractionated in high resolution onto 384-well plates using liquid chromatography followed by coagulopathic bioassaying of the obtained fractions. Bioassay activities were correlated to parallel recorded mass spectrometric and proteomics data to assign the venom toxins responsible for coagulopathic activity and assess which of these toxins could be neutralized by the inhibitors under investigation. Our results showed that the phospholipase A ₂ -inhibitor varespladib neutralized the vast majority of anticoagulation activities found across all of the tested snake venoms. Of the snake venom metalloproteinase inhibitors, marimastat demonstrated impressive neutralization of the procoagulation activities detected in all of the tested venoms, whereas dimercaprol and DMPS could only partially neutralize these activities at the doses tested. Our results provide additional support for the concept that combination of small molecules, particularly the combination of varespladib with marimastat, serve as a drug-repurposing opportunity to develop new broad-spectrum inhibitor-based therapies for snakebite envenoming.

Anacondas, genus Eunectes, are a group of aquatic snakes with a wide distribution in South America. The taxonomic status of several species has been uncertain and/or controversial. Using genetic data from four recognized anaconda species across nine countries, this study investigates the phylogenetic relationships within the genus Eunectes. A key finding was the identification of two distinct clades within Eunectes murinus, revealing two species as cryptic yet genetically deeply divergent. This has led to the recognition of the Northern Green Anaconda as a separate species (Eunectes akayima sp. nov), distinct from its southern counterpart (E. murinus), the Southern Green Anaconda. Additionally, our data challenge the current understanding of Yellow Anaconda species by proposing the unification of Eunectes deschauenseei and Eunectes beniensis into a single species with Eunectes notaeus. This reclassification is based on comprehensive genetic and phylogeographic analyses, suggesting closer relationships than previously recognized and the realization that our understanding of their geographic ranges is insufficient to justify its use as a separation criterion. We also present a phylogeographic hypothesis that traces the Miocene diversification of anacondas in western South America. Beyond its academic significance, this study has vital implications for the conservation of these iconic reptile species, highlighting our lack of knowledge about the diversity of the South American fauna and the need for revised strategies to conserve the newly identified and reclassified species.

While elucidating the evolutionary trajectory of green anacondas, we previously documented the existence of two distinct species, Eunectes akayima sp. nov. and Eunectes murinus (Linnaeus, 1758), that separated approximately 10 million years ago. Our research integrates a novel molecular clock approach, focuses on tectonic plate movements with fossil records as minimal chronological markers, and offers a refined understanding of speciation events in relation to major biogeographical occurrences in South America. Mitochondrial DNA analysis demonstrates a significant genetic divergence between the species, which is supported by a notable difference in sexual size dimorphism (SSD) intensity between the two species, along with other morphological differences. This paper also rectifies earlier oversights in the description of the new species and clarifies taxonomic ambiguities in compliance with the International Code of Zoological Nomenclature (henceforth ICZN). In addition, we designate a neotype for E. murinus to stabilize the group. In an effort to honor Indigenous nations, E. akayima sp. nov. derives its name from the Carib language, advocating for the inclusion of traditional names in scientific discourse. Our paper not only contributes to the taxonomic stability of anacondas but also advocates for the usage of Indigenous names in zoological nomenclature by adopting a more inclusive and flexible approach to the ICZN and eliminating unintended exclusionary practices that we have inherited in science as in other disciplines.