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

Autoren

Silvia Schwarz
Daniel Sauter
Kai Wang
Ronghua Zhang
Bing Sun
Anastasia Karioti
Anna Bilia
Thomas Efferth
Wolfgang Schwarz

DOI

10.1055/s-0033-1360277

eISSN

1439-0221

ISSN

0032-0943

Ausgabe der Veröffentlichung

02/03

Zeitschrift

Planta Medica

Sprache

en

Online publication date

2014

Paginierung

177 - 182

Status

Published online

Herausgeber

Georg Thieme Verlag KG

Herausgeber URL

http://dx.doi.org/10.1055/s-0033-1360277

Datum der Datenerfassung

2017

Titel

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

Ausgabe der Zeitschrift

80

Data source: Crossref

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.

Addresses

Shanghai Research Center for Acupuncture & Meridians, Shanghai, China.

Autoren

Silvia Schwarz
Daniel Sauter
Kai Wang
Ronghua Zhang
Bing Sun
Anastasia Karioti
Anna Rita Bilia
Thomas Efferth
Thomas Efferth
Wolfgang Schwarz

DOI

10.1055/s-0033-1360277

eISSN

1439-0221

Externe Identifier

PubMed Identifier: 24458263
PubMed Central ID: PMC7171712

Open access

true

ISSN

0032-0943

Ausgabe der Veröffentlichung

2-3

Zeitschrift

Planta medica

Schlüsselwörter

Animals
Xenopus
Kaempferols
Viral Proteins
Viral Envelope Proteins
Antiviral Agents
Patch-Clamp Techniques
Viroporin Proteins
Severe acute respiratory syndrome-related coronavirus

Sprache

eng

Medium

Print-Electronic

Online publication date

2014

Open access status

Open Access

Paginierung

177 - 182

Datum der Veröffentlichung

2014

Status

Published

Datum der Datenerfassung

2014

Titel

Kaempferol derivatives as antiviral drugs against the 3a channel protein of coronavirus.

Sub types

Research Support, Non-U.S. Gov't
research-article
Journal Article

Ausgabe der Zeitschrift

80

Files

http://www.thieme-connect.de/products/ejournals/pdf/10.1055/s-0033-1360277.pdf https://europepmc.org/articles/PMC7171712?pdf=render

Data source: Europe PubMed Central

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.

Autoren

Silvia Schwarz
Daniel Sauter
Kai Wang
Ronghua Zhang
Bing Sun
Anastasia Karioti
Anna Rita Bilia
Thomas Efferth
Wolfgang Schwarz

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/24458263

DOI

10.1055/s-0033-1360277

eISSN

1439-0221

Externe Identifier

PubMed Central ID: PMC7171712

Ausgabe der Veröffentlichung

2-3

Zeitschrift

Planta Med

Schlüsselwörter

Animals
Antiviral Agents
Kaempferols
Patch-Clamp Techniques
Severe acute respiratory syndrome-related coronavirus
Viral Envelope Proteins
Viral Proteins
Viroporin Proteins
Xenopus

Sprache

eng

Country

Germany

Paginierung

177 - 182

Datum der Veröffentlichung

2014

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2014

Titel

Kaempferol derivatives as antiviral drugs against the 3a channel protein of coronavirus.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

80

Data source: PubMed

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

Files

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