Antifungal drug discovery: the process and outcomes
Richard Calderone,Nuo Sun,Francoise Gay-Andrieu,William C. Groutas,Pathum M. Weerawarna,Sridhar Prasad,Deepu Alex,Dongmei Li +7 more
TLDR
The dogma on antifungal discovery is examined and it is suggested that a major thrust in technologies such as structural biology, homology modeling and virtual imaging is needed to drive discovery.Abstract:
Abstr A ct: New data suggest that the global incidence of several types of fungal diseases have traditionally been under-documented. Of these, mortality caused by invasive fungal infections remains disturbingly high, equal to or exceeding deaths caused by drug-resistant tuberculosis and malaria. It is clear that basic research on new antifungal drugs, vaccines and diagnostic tools is needed. In this review, we focus upon antifungal drug discovery including in vitro assays, compound libraries and approaches to target identification. Genome mining has made it possible to identify fungal-specific targets; however, new compounds to these targets are apparently not in the antimicrobial pipeline. We suggest that ‘repurposing’ compounds (off patent) might be a more immediate starting point. Furthermore, we examine the dogma on antifungal discovery and suggest that a major thrust in technologies such as structural biology, homology modeling and virtual imaging is needed to drive discovery.read more
Citations
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Ecology of aspergillosis: insights into the pathogenic potency of Aspergillus fumigatus and some other Aspergillus species
Caroline Paulussen,John E. Hallsworth,Sergio Álvarez-Pérez,William C. Nierman,Philip G Hamill,David Blain,Hans Rediers,Bart Lievens +7 more
TL;DR: The biophysical capabilities of Aspergillus pathogens, key aspects of their ecophysiology and the flexibility to undergo a sexual cycle or form cryptic species are focused on.
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History of the development of antifungal azoles: A review on structures, SAR, and mechanism of action.
TL;DR: This review summarized the state-of-the-art information about azole drugs, with a specific focus on those in the pipelines of pharmaceutical companies, into four generations with regard to their structural similarity, and highlights information on the structure activity relationship (SAR), target description, hybrid antifungal agents as possible future generation.
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Combined Antifungal Resistance and Biofilm Tolerance: the Global Threat of Candida auris.
Ryan Kean,Gordon Ramage +1 more
TL;DR: The clinical importance of antifungal resistance in C. auris is highlighted and the current understanding of the mechanisms associated with azole, polyene, and echinocandin resistance is explored.
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The Antifungal Activity of Naphthoquinones: An Integrative Review
Débora Omena Futuro,Patricia G. Ferreira,Caroline D. Nicoletti,Luana Pereira Borba-Santos,Fernando de C. da Silva,Sonia Rozental,Vitor F. Ferreira +6 more
TL;DR: The objective of this review is to describe the development of naphthoquinones as antifungals for the treatment of Candida species and to note the most promising compounds.
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System-level impact of mitochondria on fungal virulence: to metabolism and beyond
TL;DR: A review of likely mechanisms of mitochondrial impact on fungal virulence pathways through metabolism and stress responses, but also potentially via control over signaling pathways, and highlights fungal mitochondrial proteins that lack human homologs and which could be inhibited as a novel approach to antifungal drug strategy.
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