Abstract
Animal venoms are promising sources of novel drug leads, but their translational potential is hampered by the low success rate of earlier biodiscovery programs, in part reflecting the narrow selection of targets for investigation. To increase the number of lead candidates, here we discuss a phylogeny-guided approach for the rational selection of venomous taxa, using tarantulas (family Theraphosidae) as a case study. We found that previous biodiscovery programs have prioritized the three subfamilies Ornithoctoninae, Selenocosmiinae, and Theraphosinae, which provide almost all of the toxin sequences currently available in public databases. The remaining subfamilies are poorly represented, if at all. These overlooked subfamilies include several that form entire clades of the theraphosid life tree, such as the subfamilies Eumenophorinae, Harpactirinae, and Stromatopelminae, indicating that biodiversity space has not been covered effectively for venom biodiscovery in Theraphosidae. Focusing on these underrepresented taxa will increase the likelihood that promising candidates with novel structures and mechanisms of action can be identified in future bioprospecting programs.
Highlights
Nature abounds with bioactive molecules synthesized by species that interact with each other, either competitively or cooperatively
Bioactive are often of 10 sourced from microbes and plants, but attention has2 turned more recently to animal venoms. These evolved for hunting prey, defense against predation, and Bioactive molecules are often sourced from microbes and plants, but attention has turned more intraspecific competition [2]
Given the clear bias in the coverage of toxin sequences and the plethora of toxins anticipated in these three underrepresented clades, plus their evolutionary distance from other tarantula subfamilies, we propose that the members of these clades should be prioritized in future bioprospecting studies
Summary
Nature abounds with bioactive molecules synthesized by species that interact with each other, either competitively or cooperatively. The in-depth survey of venoms and their components has already recently to animal venoms These evolved for hunting prey, defense against predation, and led to the development of several important drugs, such as the analgesic ziconotide from the cone intraspecific competition [2]. The in-depth survey of venoms and their components has already led snail Conus magus, the antidiabetic exenatide, a synthetic derivative of exendin-4 from venom of to the development of several important drugs, such as the analgesic ziconotide from the cone snail theConus beaded-lizard. Thismost means that the vast of majority of venomous or arachnids being examples Representatives these groups have species remain virtually not yet been studied forunexploited their venom[4]. Given that stability in vivo stability in vivo and target specificity are major constraints for suitable drug candidates, facing the and target specificity are major constraints for suitable drug candidates, facing the sheer diversity of peptides in spider venom, it is clear that it likely harbors several yet to be discovered biologics that will almost certainly serve as drug leads in the future
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