Figure 1.

Cellular targets for anti-influenza drugs in the context of the replication cycle of influenza virus. Stages of influenza A virus replication are in green. Cellular pathways shown by siRNA screens to be essential for completion of the viral replication cycle are shown in red. The influenza A virus protein hemagglutinin binds to sialylated glycoprotein receptors on the host-cell surface and enters the cell by receptor-mediated endocytosis. Following internalization and endosomal acidification, which permits fusion of the host and viral membranes by altering the conformation of hemagglutinin, viral ribonucleoproteins (RNPs; dark blue) are released in the cytoplasm. In the nucleus of infected cells, the viral RNAs are transcribed into mRNAs and replicated by the viral RNA–dependent RNA polymerase complex. The newly synthesized viral RNPs are exported into the cytoplasm and, after assembly, mature virions bud from the cell surface. Currently, the viral M2 ion channel protein and neuraminidase are the only two targets of influenza antiviral drugs (gray boxes) licensed by the US Food and Drug Administration. Adamantane drugs, which include amantadine and rimantadine, block the action of the viral M2 protein during uncoating of the virus. Zanamivir and oseltamivir target neuraminidase, which is required for release of progeny virus from the cell surface. Adapted from ref. 13.