Venom back in vogue as a wellspring for drug candidates

Abstract

Pediatric neurosurgeon Amy Lee works by the small, bright light of a microscope, her gaze focused on the opened skull of a child. Lee moves her hands calmly and confidently over the exposed brain, plucking out as much tumor as she safely can.But there are some surgeries, and some parts of the brain, where tumor tissue and healthy tissue look very much alike. In those cases, Lee, based at Seattle Children's Hospital in Washington, looks to a computer monitor beside the operating table, where a view of the brain shows tumor, illuminated in fluorescent green, nestled in otherwise white, healthy tissue. This new diagnostic tool helps surgeons gauge, in real time, how much tumor they've removed, and how much is left behind.That green glow comes from tozuleristide, a new diagnostic drug in phase two clinical trials. But the drug's novelty stems not only from its potential to highlight troublesome childhood tumors, but also from the compound's source: the potent venom of the Israeli deathstalker scorpion (Leiurus quinquestriatus).Tozuleristide uses a peptide from the venom and an infrared dye to seek out and illuminate tumors of all kinds, including in the breast, colon, and skin. The drug has gone through safety testing and early clinical trials to image brain tumors in children, and today stands about two years from possible US Food and A handful of promising new drug candidates are derived from peptides in the venom of scorpions and other animals. Image credit: Shutterstock/Bens_Hikes.

Targeting Cannabinoid Receptors: Current Status and Prospects of Natural Products

“…Moreover, the advancement of technologies has enabled the study of venoms from animals that are small, rare, or hard to maintain in the lab, which greatly facilitates the high-throughput screening of animal venoms and the characterization of venom peptides’ structure and function [ 38 ]. The research on venom-derived drugs has so far yielded at least 10 registered and deposited drugs on the market [ 165 ], examples of which include captopril (Capoten ® ), tirofiban (Aggrastat ® ) and eptifibatide (Integrilin ® ). Although humans have been using venoms for thousands of years, only for the past five or six decades scientists have been studying the venoms at the molecular level using modern biochemistry, physiology and biophysics and other technologies [ 38 ].…”

Targeting tumor resistance mechanisms

“…There is a compelling need for an innovative ligand design 90 . Perhaps one way out would consist of putting more effort toward the characterization of venoms 91 , 92 . It is estimated that 200,000 venomous species exist, which represent around 40 million toxins; of these, fewer than 5,000 have been pharmacologically characterized.…”

“…Venomics—which integrate genomic, transcriptomic, and proteomic approaches to the study of venoms—is gaining interest as a strategy for drug discovery 93 – 95 . Tozuleristide uses chlorotoxin, a 36–amino acid peptide isolated from the venom of the deathstalker scorpion Leiurus quinquestriatus , and an infrared dye 92 . It is being evaluated as a new diagnostic drug in a phase II/III clinical trial to determine how well the drug can help distinguish between tumor and normal tissue during surgery in pediatric primary central nervous system tumors (NCT03579602).…”

Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus

“…Consequently, venom components have become highly specialized with the ability to perform complex and intricate biochemical tasks within their target organism [2]. This ability to precisely manipulate specific organismal functions presents a biochemical gold mine of bio-active compounds that can be developed towards therapeutic or biotechnological applications [3,4].…”