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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
1   Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Vienna, Austria
,
Christina E. Mair
1   Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Vienna, Austria
,
Johannes Kirchmair
2   Center for Bioinformatics, Department of Informatics, MIN Faculty, Universität Hamburg, Hamburg, Germany
,
Michaela Schmidtke
3   Section of Experimental Virology, Department of Medical Microbiology, Jena University Hospital, Jena, Germany
,
Judith M. Rollinger
1   Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Vienna, Austria
› Author Affiliations
Further Information

Publication History

received 16 November 2017
revised 01 March 2018

accepted 07 March 2018

Publication Date:
19 March 2018 (online)

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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

* Dedicated to “Women in Natural Products Science”.


Supporting Information

    References to the origin and voucher specimens of the natural materials (deposited in the herbarium) including their registration numbers (Table 1S), data leading to the determination of the IC50s/CC50s (individual and means) as well as their confidence intervals (Table 2S) and graphs depicting dose-dependencies (Fig. 1S) for the most active extracts and further investigated extracts, and chromatograms of HPLC analyses and structures of main constituents for the most relevant extracts (Figs. 2S–9S) are available as Supporting Information.

  • Supporting Information
 

  • References

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