Coronaviral Ion Channels as Target for Chinese Herbal Medicine

Abstract

A variety of viruses encode for proteins that can form ion channels in the membrane of infected cells. For example, the protein coded by the open-reading-frame 3a of SARS coronavirus (SARS-CoV) has been demonstrated to form a cation-selective channel that may become expressed in the infected cell, and its activation is then involved in virus release. Chinese herbal drugs that inhibit the ion channel formed by the 3a protein can be expected to inhibit virus release, and therefore they are a source for the development of novel therapeutic agents. Various drugs found in Chinese herbs are well known as anticancer agents and also have antiviral potency. In one study we tested some of them with respect to their potency to block the 3a channel. Application of the anthraquinone emodin was used as adjunct therapy in treatment of SARS, and we have demonstrated that it can inhibit the 3a ion channel as well as virus release with a K1/2 value of approximately 20 µM. Also the flavonols kaempferole and kaempferole glycosides may be potent inhibitors of the 3a channels. On the other hand, the favonol quercitin seems not to be effective. In addition, the flavanon naringenin and the isoflavon genistein were ineffective in inhibiting 3a-mediated currents. Antiviral activity of the artemisinin derivative artesunate is well documented, but we did not detect any inhibition of 3a-mediated currents. We suggest that viral ion channels, in general, may be good targets for the development of antiviral agents, and that, in particular, emodin and kaempferol gycosides are good candidates for 3a channel proteins in coronaviruses.