Chemical Biology Group, Luxembourg Centre for Systems Biomedicine, Belvaux, Luxembourg
Secondary metabolites from marine organisms are structurally diverse small molecules with high levels of bioactivity, and represent an underutilized resource for modern drug discovery. To facilitate the identification of drug-like marine metabolites, the significant potential of in vivo models of human disease – in particular those suitable for medium-throughput screening and bioassay-guided fractionation – should be explored in future marine biodiscovery efforts. It is worth noting that the 2015 Nobel Prize in Physiology or Medicine was awarded for the discovery and development of two different natural product-based medicines – artemisin and an avermectin derivative – that were both identified by phenotype-based in vivo screening. As an alternative to both target-based drug discovery and in vitro cell-based high-content screening, in vivo bioassays enable biodiscovery screening within a whole-organism context, thereby significantly increasing the biomedical relevance of bioactive marine metabolites identified in this manner. The higher predictivity offered by in vivo bioassays ensures that these compounds have a higher chance of being validated in subsequent preclinical proof-of-concept studies using mammalian models. The throughput of certain in vivo bioassays – in particular, those using C. elegans, Drosophila and zebrafish models of human disease – is sufficiently high to be able to efficiently screen all currently available marine extracts and pure metabolites available within the marine biodiscovery community. By continuing to explore synergies and possible collaborations between research groups in the marine biodiscovery and model organism communities, new opportunities will emerge to systematically interrogate the unique chemical space offered by marine organisms against a growing panel of disease-relevant in vivo bioassays, resulting in many exciting discoveries and novel drug leads in the years to come.