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 Ba2+ with a K1/2 value of 1.6 mM. Therefore, we determined viral protein U-mediated current as current
component blocked by 10 mM Ba2+. 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.
Key words
flavonoids - genistein - HIV-1 - ion channel - virus release
