The 2020 winner of the Ōmura Award for original article goes to the authors of an outstanding paper on the development of a practical method for the identification of bioactive components from fungal cultures, entitled ‘Enhanced dereplication of fungal cultures via use of mass defect filtering’ by Paguigan et al. [1]. Efficient and accurate dereplication of antibiotic substances from crude extracts is a critical aspect of natural product discovery. The study by Paguigan et al. outlines a robust strategy for this using heated electrospray ionisation to save chromatography time and couples the approach with mass defect filtering to rapidly identify structurally related components within a complex sample (Fig. 1). Mass defect filtering is a data mining technique that can be applied after an active component is identified to look for related substances that share a central core. The method is used in other areas of pharmacology, notably drug metabolism studies, and can be applied retrospectively to high-resolution mass spectrum ion-scan datasets once a central core is identified to study related secondary metabolites. The authors demonstrate the combined approach presented is robust by demonstrating its ability to detect a wide range of secondary metabolites from fungal cultures. The studies are well described, and the paper is an excellent read, especially for those interested in learning about dereplication approaches to identify bioactive substances from complex mixtures.

Fig. 1
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The mass defect filtering workflow presented by Paguigan et al. Reprinted from Paguigan, N., EL-Elimat, T., Kao, D. et al. Enhanced dereplication of fungal cultures via use of mass defect filtering. J Antibiot 70, 553–561 (2017). https://doi.org/10.1038/ja.2016.145, under a CC BY-NC-ND 4.0 license

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The Editorial Board of The Journal of Antibiotics has given the 2020 JA Ōmura Award to Andy Crump for an outstanding review article entitled “Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations” [2]. In 2015, work on ivermectin by Satoshi Ōmura and William C. Campbell was awarded the Nobel Prize in Physiology or Medicine for their discovery of a novel therapy against parasitic roundworm infections. While there are many excellent review papers on the discovery, development, and success of ivermectin as a drug against onchocerciasis and lymphatic filariasis, this review particularly focused on yet unsolved puzzles surrounding the mechanism of action and ivermectin’s vast future potential to combat other diseases that threaten human health worldwide. Ivermectin is known to induce paralysis of somatic muscles in parasites by disrupting glutamate-gated chloride channels, which do not exist in mammals. Ivermectin has also minor effects on γ-aminobutyric acid (GABA) receptors, but in mammals GABA receptors and neurons are restricted to the central nervous system. As ivermectin is unable to cross the blood-brain barrier, it remains safe for human use. However, several mysteries remain. For instance, no ivermectin-resistant parasites have emerged in the human population for over 30 years, although resistant parasites have rapidly appeared in treated animals. Despite a plasma half-life of around 12 h, the levels of dermal microfilariae were reduced for a long time after ivermectin administration, and remained extremely low for about 12 months, suggesting the involvement of other mechanisms such as immunoregulation. In addition to onchocerciasis, strongyloidiasis, and lymphatic filariasis, increasing evidence indicates that ivermectin can kill malaria, leishmania, and African Trypanosoma parasites as well as their vectors. Moreover, ivermectin’s activities in a range of very different diseases, including viral infections, have generated interest and excitement in the global health research community. Just as the review article title says, ivermectin continues to surprise us all.