Innovative omics-based approaches for prioritisation and targeted isolation of natural products - new strategies for drug discovery

The exploration of the chemical diversity of extracts from various biological sources has led to major drug discoveries. Over the past two decades, despite the introduction of advanced methodologies for natural product (NP) research (e.g., dereplication and high content screening), successful accounts of the validation of NPs as lead therapeutic candidates have been limited. In this context, one of the main challenges faced is related to working with crude natural extracts because of their complex composition and the inadequacies of classical bioguided isolation studies given the pace of high-throughput screening campaigns. In line with the development of metabolomics, genomics and chemometrics, significant advances in metabolite profiling have been achieved and have generated high-quality massive genome and metabolome data on natural extracts. The unambiguous identification of each individual NP in an extract using generic methods remains challenging. However, the establishment of structural links among NPs via molecular network analysis and the determination of common features of extract composition have provided invaluable information to the scientific community. In this context, new multi-informational-based profiling approaches integrating taxonomic and/or bioactivity data can hold promise for the discovery and development of new bioactive compounds and return NPs back to an exciting era of development. In this article, we examine recent studies that have the potential to improve the efficiency of NP prioritisation and to accelerate the targeted isolation of key NPs. Perspectives on the field's evolution are discussed.