Natural products against acute respiratory infections: Strategies and lessons learned.

A wide variety of traditional herbal remedies have been used throughout history for the treatment of symptoms related to acute respiratory infections (ARIs). The present work provides a timely overview of natural products affecting the most common pathogens involved in ARIs, in particular influenza viruses and rhinoviruses as well as bacteria involved in co-infections, their molecular targets, their role in drug discovery, and the current portfolio of available naturally derived anti-ARI drugs. Literature of the last ten years was evaluated for natural products active against influenza viruses and rhinoviruses. The collected bioactive agents were further investigated for reported activities against ARI-relevant bacteria, and analysed for the chemical space they cover in relation to currently known natural products and approved drugs. An overview of (i) natural compounds active in target-based and/or phenotypic assays relevant to ARIs, (ii) extracts, and (iii) in vivo data are provided, offering not only a starting point for further in-depth phytochemical and antimicrobial studies, but also revealing insights into the most relevant anti-ARI scaffolds and compound classes. Investigations of the chemical space of bioactive natural products based on principal component analysis show that many of these compounds are drug-like. However, some bioactive natural products are substantially larger and have more polar groups than most approved drugs. A workflow with various strategies for the discovery of novel antiviral agents is suggested, thereby evaluating the merit of in silico techniques, the use of complementary assays, and the relevance of ethnopharmacological knowledge on the exploration of the therapeutic potential of natural products. The longstanding ethnopharmacological tradition of natural remedies against ARIs highlights their therapeutic impact and remains a highly valuable selection criterion for natural materials to be investigated in the search for novel anti-ARI acting concepts. We observe a tendency towards assaying for broad-spectrum antivirals and antibacterials mainly discovered in interdisciplinary academic settings, and ascertain a clear demand for more translational studies to strengthen efforts for the development of effective and safe therapeutic agents for patients suffering from ARIs.

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