title: Genistein as antiviral drug against HIV ion channel.
abstract: Various drugs found in Chinese herbs are well known for their antiviral potency. We have tested several flavonoids with respect to their potency to block the viral protein U of the human immunodeficiency type 1 virus, which is believed to form a cation-permeable ion channel in the infected cell. We used Xenopus oocytes with heterologously expressed viral protein U as model system to test the efficacy of the drugs in voltage-clamp experiments. This method had been demonstrated in the past as a useful tool to screen drugs for their potency in inhibition of ion channel activity. The viral protein U-mediated current could be inhibited by Ba(2+) with a K1/2 value of 1.6 mM. Therefore, we determined viral protein U-mediated current as current component blocked by 10 mM Ba(2+). We screened several flavonoids with respect to their effects on this current. The flavonols quercetin and kaempferol, and the flavanols (-)epigallochatechin and (-)epichatechin were ineffective. The flavanone naringenin showed at 20 µM slight (about 10%) inhibition. The most potent drug was the isoflavon genistein which exhibited at 20 µM significant inhibition of about 40% with a K1/2 value of 81 ± 4 µM. We suggest that viral ion channels, in general, may be a good target for development of antiviral agents, and that, in particular, isoflavons may be candidates for development of drugs targeting viral protein U.
authors: Shanghai Research Center for Acupuncture & Meridians, Shanghai, China.
authors: Daniel
authors: D
authors: Sauter
authors: Shanghai Research Center for Acupuncture & Meridians, Shanghai, China.
authors: Silvia
authors: S
authors: Schwarz
authors: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors: Kai
authors: K
authors: Wang
authors: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors: Ronghua
authors: R
authors: Zhang
authors: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors: Bing
authors: B
authors: Sun
authors: Shanghai Research Center for Acupuncture & Meridians, Shanghai, China.
authors: Wolfgang
authors: W
authors: Schwarz
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression; D019833:Genistein / Q000737:chemistry / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D054298:Human Immunodeficiency Virus Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D018408:Patch-Clamp Techniques; D018075:RNA, Complementary / Q000235:genetics; D019076:Transgenes; D054334:Viral Regulatory and Accessory Proteins / Q000037:antagonists & inhibitors; D057074:Virus Release / Q000187:drug effects; D014982:Xenopus laevis; D000086082:Viroporin Proteins
chemical_list: D000998:Antiviral Agents; D044950:Flavanones; D005419:Flavonoids; D019833:Genistein; D054298:Human Immunodeficiency Virus Proteins; D007473:Ion Channels; D018075:RNA, Complementary; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins; C005273:naringenin