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In the event of an avian flu pandemic, doctors would have only two types of pills at their disposal, M2 ion channel blockers and neuraminidase inhibitors. Viruses can become resistant to both types of medication, potentially leaving the public defenseless. In an effort to improve the flu drug arsenal, Ying Guo, Yingxia Li, and colleagues of the Chinese Academy of Medical Sciences and Ocean University of China have synthesized saponin derivatives that could serve as a third class of avian flu remedy (J. Med. Chem., DOI: 10.1021/jm900275m). Saponins are natural products, some of which can act as entry inhibitors—compounds that prevent viruses from slipping into their host cells. They work by binding to hemagglutinin on the surface of viral particles, rendering the particles incapable of latching onto sialic acid, a receptor found on the surface of human cells. The team discovered its lead compound (shown) derived from an Asian yam by screening a semisynthetic compound library against lentiviruses bearing a hemagglutinin gene taken from the H5N1 virus. Several of the compounds protected human lung cells from the pseudotyped virus, the researchers report, with the trisaccharide groups on the saponins serving as crucial elements for antiviral activity.
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