Targeting inflammation and Influenza: Integration of computational methods into lead finding from natural sources

Currently the search for drug leads from natural sources is undergoing an enormous revival which is reflected by an increasing interest in developing optimized time- and cost-saving strategies guiding this endeavor. Since nature offers an infinite pool of complex scaffolds with a high chemical and biological diversity sophisticated rationales to prioritize isolation and purification efforts are of utmost importance.

Here, the successful application of a combination of several approaches including in silico techniques, ethnopharmacological knowledge, and bioactivity-guided isolation is demonstrated by two examples:

• the pharmacophore based discovery of anti-inflammatory and farnesoid X receptor (FXR)-inducing lanostane-type triterpenes from the fruit body of the traditional Chinese medicinal fungus Ganoderma lucidum (Curtis) P. Karst. (Ganodermataceae), and

• the identification and in silico binding mode studies of a diarylheptanoid isolated from the seed extract of Alpinia katsumadai Hayata (Zingiberaceae) as an innovative influenza neuraminidase (NA) inhibitor.

Finally, pitfalls and challenges of these strategies will be discussed in respect to future applications.