Julia Langeder1, Ulrike Grienke2, Ya Chen3, Johannes Kirchmair4, Michaela Schmidtke5, Judith M Rollinger1. 1. Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Althanstraße 14, 1090, Vienna, Austria. 2. Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Althanstraße 14, 1090, Vienna, Austria. Electronic address: ulrike.grienke@univie.ac.at. 3. University of Hamburg, Center for Bioinformatics (ZBH), Bundesstraße 43, 22763, Hamburg, Germany. 4. Department of Chemistry, University of Bergen, N-5020, Bergen, Norway; Computational Biology Unit (CBU), University of Bergen, N-5020, Bergen, Norway. 5. Section of Experimental Virology, Department of Medical Microbiology, Jena University Hospital, Hans-Knöll-Straße 2, Jena, 07745, Germany.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: A wide variety of traditional herbal remedies have been used throughout history for the treatment of symptoms related to acute respiratory infections (ARIs). AIM OF THE REVIEW: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
ETHNOPHARMACOLOGICAL RELEVANCE: A wide variety of traditional herbal remedies have been used throughout history for the treatment of symptoms related to acute respiratory infections (ARIs). AIM OF THE REVIEW: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Dâmaris Silveira; Jose Maria Prieto-Garcia; Fabio Boylan; Omar Estrada; Yris Maria Fonseca-Bazzo; Claudia Masrouah Jamal; Pérola Oliveira Magalhães; Edson Oliveira Pereira; Michal Tomczyk; Michael Heinrich Journal: Front Pharmacol Date: 2020-09-23 Impact factor: 5.810