Challenges in the discovery of natural products effective against acute respiratory infections

According to the WHO, lower respiratory tract infections are the fourth most common cause of death globally and the first cause in low-income economies. Mainly caused by influenza viruses and rhinoviruses, lethality is heavily boosted by co-infection with S. pneumoniae and S. aureus. The efficacy of antiviral drugs (e.g. neuraminidase inhibitors, NAIs) and antibiotics is hampered by resistance issues. Remarkably, herbal remedies have been successfully used to reduce respiratory symptoms throughout history.

In a recently finalized project, we used this empirical knowledge for the selection of natural materials for antimicrobial studies, optimized our extraction protocol to avoid testing of promiscuous compounds, and explored the strengths and limitations of cell-based, target-based, and/or in silico strategies to evaluate the antimicrobial potential of 162 natural extracts.

As a result, we have established activity/cytotoxicity thresholds and a protocol to discriminate between antiviral and dual-active agents and to characterize their mechanism of action [1], [2]. Further, a screening platform as tool for the identification of novel NAIs and their antimicrobial profiling was established [3]. Our workflow applying a previously adapted extraction protocol for extracts and isolated natural compounds uses a sophisticated set of different assays, which enables us to (i) recognize caveats, (ii) circumvent pitfalls related to assay interferences, and thus to (iii) generate reliable data on natural products targeting acute respiratory infections.

• References

• 1 Grienke U, Mair CE, Kirchmair J, Schmidtke M, Rollinger JM. Discovery of bioactive natural products for the treatment of acute respiratory infections - an integrated approach. Planta Med 2018; 84: 684-695.
• 2 Richter M, Schumann L, Walther E, Hoffmann A, Braun H, Grienke U. et al. Complementary assays helping to overcome challenges for identifying neuraminidase inhibitors. Future Virol 2015; 10: 77-88.
• 3 Hoffmann A, Schade D, Kirchmair J, Clement B, Sauerbrei A, Schmidtke M. Platform for determining the inhibition profile of neuraminidase inhibitors in an influenza virus N1 background. J Virol Methods 2016; 237: 192-199.