Implementation of Traditional Medicine into Structure-Based Approaches for Antiviral Lead Discovery

The search for new drug leads against viruses remains an area of active investigations. In the last decades the influenza neuraminidase (iNA) has been extensively exploited by computational approaches in the search for small molecule inhibitors of this key enzyme responsible for viral replication and spread. These efforts fueled the development of currently worldwide licensed iNA inhibitors. However, the increase of drug-resistant influenza virus strains demonstrates the urgent need for innovative and effective antiviral agents. It is anticipated that the recent findings of the enzyme's flexibility and thereby extended binding pocket will help to overcome these hindrances.¹

In our lab several virtual screening campaigns on 3D natural product databases have proven to be highly efficient for the target-oriented identification of bioactive candidates. Integration of these heuristic approaches with empirical ones, such as from traditional medicine and in vitro extract screening, are helpful strategies for molecular understanding and prioritizing compounds to be isolated from natural sources. Application examples will be presented for the discovery of ligands of the hydrophobic pocket in the rhinoviral capsid² and the extended binding pocket of iNA.^1,3

¹ Kirchmair, J. et al. (2011) Future Med. Chem. 3: 437; ² Rollinger, J. M. et al. (2008)J. Med. Chem. 51: 842; ³ Grienke, U. et al. (2010)J. Med. Chem. 53: 778 – 786.

Acknowledgements: Supported by the Austrian Science Fund (FWF P24587)