title: Antifungal drug discovery: the process and outcomes.
abstract: 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.
authors.affiliation: Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Calderone
authors.forename: Nuo
authors.initials: N
authors.lastname: Sun
authors.forename: Francoise
authors.initials: F
authors.lastname: Gay-Andrieu
authors.forename: William
authors.initials: W
authors.lastname: Groutas
authors.forename: Pathum
authors.initials: P
authors.lastname: Weerawarna
authors.forename: Sridhar
authors.initials: S
authors.lastname: Prasad
authors.forename: Deepu
authors.initials: D
authors.lastname: Alex
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D009181:Mycoses / Q000188:drug therapy*
chemical_list: D000935:Antifungal Agents
keywords: antifungals; compound libraries; discovery; drug targets; repurposing