Kaempferol derivatives as antiviral drugs against the 3a channel protein of coronavirus.
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.
Shanghai Research Center for Acupuncture & Meridians, Shanghai, China.
Silvia
S
Schwarz
Shanghai Research Center for Acupuncture & Meridians, Shanghai, China.
Daniel
D
Sauter
Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Chinese Academy of Sciences, Shanghai, China.
Kai
K
Wang
Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Chinese Academy of Sciences, Shanghai, China.
Ronghua
R
Zhang
Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Chinese Academy of Sciences, Shanghai, China.
Bing
B
Sun
Department of Chemistry, Building of Pharmaceutical Sciences, University of Florence, Sesto Fiorentino (FI), Italy.
Anastasia
A
Karioti
Department of Chemistry, Building of Pharmaceutical Sciences, University of Florence, Sesto Fiorentino (FI), Italy.
Anna Rita
AR
Bilia
Institute for Pharmacology and Biochemistry, J-Gutenberg University, Mainz, Germany.
Thomas
T
Efferth
Shanghai Research Center for Acupuncture & Meridians, Shanghai, China.
Wolfgang
W
Schwarz
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D044949:Kaempferols / Q000737:chemistry / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D045473:Severe acute respiratory syndrome-related coronavirus; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000086082:Viroporin Proteins; D014981:Xenopus
C487105:3a protein, SARS-CoV; D000998:Antiviral Agents; D044949:Kaempferols; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D000086082:Viroporin Proteins