Covering: 2000 to 2011 The imminent threat of influenza pandemics and repeatedly reported emergence of new drug-resistant influenza virus strains demonstrate the urgent need for developing innovative and effective antiviral agents for prevention and treatment. At present, influenza neuraminidase (NA), a key enzyme in viral replication, spread, and pathogenesis, is considered to be one of the most promising targets for combating influenza. Despite the substantial medical potential of NA inhibitors (NAIs), only three of these drugs are currently on the market (zanamivir, oseltamivir, and peramivir). Moreover, sudden changes in NAI susceptibility revealed the urgent need in the discovery/identification of novel inhibitors. Nature offers an abundance of biosynthesized compounds comprising chemical scaffolds of high diversity, which present an infinite pool of chemical entities for target-oriented drug discovery in the battle against this highly contagious pathogen. This review illuminates the increasing research efforts of the past decade (2000–2011), focusing on the structure, function and druggability of influenza NA, as well as its inhibition by natural products. Following a critical discussion of publications describing some 150 secondary plant metabolites tested for their inhibitory potential against influenza NA, the impact of three different strategies to identify and develop novel NAIs is presented: (i) bioactivity screening of herbal extracts, (ii) exploitation of empirical knowledge, and (iii) computational approaches. This work addresses the latest developments in theoretical and experimental research on properties of NA that are and will be driving anti-influenza drug development now and in the near future.

Polypores have been applied in traditional Chinese medicine up to the present day, and are becoming more and more popular worldwide. They show a wide range of bioactivities including anti-cancer, anti-inflammatory, antiviral and immuno-enhancing effects. Their secondary metabolites have been the focus of many studies, but the importance of fungal strain for bioactivity and metabolite production has not been investigated so far for theseBasidiomycetes. Therefore, we screened several strains from three medicinal polypore species from traditional European medicine:Fomes fomentarius, Fomitopsis pinicolaandPiptoporus betulinus.A total of 22 strains were compared concerning their growth rates, optimum growth temperatures, as well as antimicrobial and antifungal properties of ethanolic fruit body extracts. The morphological identification of strains was confirmed based on rDNA ITS phylogenetic analyses. Our results showed that species delimitation is critical due to the presence of several distinct lineages, e.g. within theFomes fomentariusspecies complex. Fungal strains within one lineage showed distinct differences in optimum growth temperatures, in secondary metabolite production, and accordingly, in their bioactivities. In general,F. pinicolaandP. betulinusextracts exerted distinct antibiotic activities againstBacillus subtilisandStaphylococcus aureusat minimum inhibitory concentrations (MIC) ranging from 31-125 μg mL⁻¹; The antifungal activities of all three polypores againstAspergillus flavus, A. fumigatus, Absidia orchidisandCandida kruseiwere often strain-specific, ranging from 125-1000 μg mL⁻¹. Our results highlight that a reliable species identification, followed by an extensive screening for a ‘best strain’ is an essential prerequisite for the proper identification of bioactive material.