Poster Presentation First Malaria World Congress 2018

Arthropod venoms: a new source of natural products for antimalarial drug discovery (#466)

Samantha Nixon 1 2 , Eva Hesping 3 , Hannah Wissing 3 , Volker Herzig 1 , Andrew C Kotze 2 , Katherine T Andrews 3 , Glenn F King 1
  1. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
  2. CSIRO Agriculture and Food, Brisbane, Queensland, Australia
  3. Griffith Institute for Drug Discovery, Griffith University , Brisbane, Queensland, Australia

Malaria remains one of the most serious parasitic diseases of humans, causing an estimated 445,000 deaths in 2016. New drugs are urgently required as resistance has emerged to all antimalarials. Venoms have evolved over millions of years to become complex cocktails of selective and potent bioactive molecules. However, their use in antimalarial drug discovery has been relatively unexplored to date. One example is scorpine from Pandinus imperator scorpion venom, which inhibits both Plasmodium berghei ookinete and P. falciparum intraerythrocytic development. Scorpine is comprised of a linear N-terminal cecropin-like domain and a C-terminal defensin-like domain. Other scorpine-like peptides exhibit independent bifunctionality in their respective linear and disulfide domains. However, the relative contributions of scorpine’s domains to its antimalarial activity are unknown. We aim to produce whole scorpine and the two domains independently to investigate these structure-activity relationships against P. falciparum. The results of this study can enable future rational drug design efforts. We are also investigating arthropod venoms more broadly for novel antimalarial compounds. We have conducted the largest ever screen of venoms against the virulent human malarial parasite, P. falciparum. Crude venoms from 234 diverse species of arthropods, including spiders, scorpions, centipedes and assassin bugs were screened in [3H]-Hypoxanthine uptake growth inhibition assay in vitro. We found 27 venoms active at 8 µg/ml (11.5% hit rate). The hits were found in spiders (including 17 tarantulas and 2 funnel-webs), 7 scorpions and a centipede species. We selected the most potent and diverse species as candidates and are using bioassay-guided fractionation to identify and characterise the active compounds. These findings indicate that arthropod venoms may be a useful source for antimalarial drug discovery.