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Planta Med 2014; 80(02/03): 177-182
DOI: 10.1055/s-0033-1360277
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Kaempferol Derivatives as Antiviral Drugs against the 3a Channel Protein of Coronavirus

Silvia Schwarz
1   Shanghai Research Center for Acupuncture & Meridians, Shanghai, China
,
Daniel Sauter
1   Shanghai Research Center for Acupuncture & Meridians, Shanghai, China
2   Institute for Biophysics, JW-Goethe-University, Frankfurt a. M., Germany
,
Kai Wang
3   Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Chinese Academy of Sciences, Shanghai, China
,
Ronghua Zhang
3   Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Chinese Academy of Sciences, Shanghai, China
,
Bing Sun
3   Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Chinese Academy of Sciences, Shanghai, China
,
Anastasia Karioti
4   Department of Chemistry, Building of Pharmaceutical Sciences, University of Florence, Sesto Fiorentino (FI), Italy
,
Anna Rita Bilia
4   Department of Chemistry, Building of Pharmaceutical Sciences, University of Florence, Sesto Fiorentino (FI), Italy
,
Thomas Efferth
5   Institute for Pharmacology and Biochemistry, J-Gutenberg University, Mainz, Germany
,
Wolfgang Schwarz
1   Shanghai Research Center for Acupuncture & Meridians, Shanghai, China
2   Institute for Biophysics, JW-Goethe-University, Frankfurt a. M., Germany
› Author Affiliations
Further Information

Publication History

received 14 September 2013
revised 02 December 2013

accepted 13 December 2013

Publication Date:
23 January 2014 (online)

Also available at
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Abstract

The protein coded by the open-reading-frame 3a of SARS coronavirus has been demonstrated to form a cation-selective channel that may become expressed in the infected cell. The activity of the channel is involved in the mechanism of virus release. Drugs that inhibit the ion channel can, therefore, inhibit virus release, and they could be a source for development of novel therapeutic antiviral agents. Various drugs found in Chinese herbs that are well known as anticancer agents also have an antiviral potency. Here we tested the flavonols kaempferol, kaempferol glycosides, and acylated kaempferol glucoside derivatives with respect to their potency to block the 3a channel. We used the Xenopus oocyte with a heterologously expressed 3a protein as a model system to test the efficacy of the flavonols. Some of these drugs turned out to be potent inhibitors of the 3a channel. The most effective one was the glycoside juglanin (carrying an arabinose residue) with an IC50 value of 2.3 µM for inhibition of the 3a-mediated current. Kaempferol derivatives with rhamnose residue also seem to be quite effective. We suggest that viral ion channels, in general, may be a good target for the development of antiviral agents, and that, in particular, kaempferol glycosides are good candidates for 3a channel proteins of coronaviruses.

Key words

coronavirus - virus release - ion channel - kaempferol derivatives - flavonoids
 

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