Discovery of Bioactive Natural Products for the Treatment of Acute Respiratory Infections – An Integrated Approach

Ulrike Grienke; Christina E. Mair; Johannes Kirchmair; Michaela Schmidtke; Judith M. Rollinger

doi:10.1055/a-0590-5153

Planta Medica, Table of Contents

Planta Med 2018; 84(09/10): 684-695
DOI: 10.1055/a-0590-5153

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Discovery of Bioactive Natural Products for the Treatment of Acute Respiratory Infections – An Integrated Approach^[*]

Ulrike Grienke

¹Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Vienna, Austria

,

Christina E. Mair

¹Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Vienna, Austria

,

Johannes Kirchmair

²Center for Bioinformatics, Department of Informatics, MIN Faculty, Universität Hamburg, Hamburg, Germany

,

Michaela Schmidtke

³Section of Experimental Virology, Department of Medical Microbiology, Jena University Hospital, Jena, Germany

,

Judith M. Rollinger

¹Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Vienna, Austria

› Author Affiliations

Abstract

In this work, an integrated approach for the identification of new antiviral agents from natural sources for the treatment of acute respiratory infections is presented. The approach comprises (i) the selection of starting material based on traditional knowledge, (ii) phenotypic screening of extracts for antiviral activity, and (iii) the implementation of in silico predictions to identify antiviral compounds and derive the molecular mechanism underlying their biological activity. A variety of starting materials from plants and fungi was selected for the production of 162 extracts. These extracts were tested in cytopathic effect inhibition assays against influenza virus A/Hong Kong/68 (HK/68), rhinovirus A2 (RV-A2), and coxsackie virus B3 (CV-B3). All extracts were also evaluated regarding their cytotoxicity. At an IC₅₀ threshold of 50 µg/mL, 20, 11, and 14% of all tested extracts showed antiviral activity against HK/68, CV-B3, and RV-A2, respectively. Among all active extracts (n = 47), 68% showed antiviral activity against one of the investigated viruses, whereas 31% inhibited at least two viruses. Herein, we present a comprehensive dataset of probed extracts along with their antiviral activities and cytotoxicity. Application examples presented in this work illustrate the phytochemical workflow for the identification of antiviral natural compounds. We also discuss the challenges, pitfalls, and advantages of the integrated approach.

Key words

antiviral - influenza - neuraminidase - ethnopharmacology - phenotypic screening

Full Text

References

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Supplementary Material

Supporting Information

Discovery of Bioactive Natural Products for the Treatment of Acute Respiratory Infections – An Integrated Approach[*]

Discovery of Bioactive Natural Products for the Treatment of Acute Respiratory Infections – An Integrated Approach^[*]