Figure 2. Inhibition of the influenza-virus replication cycle by antiviral agents.

After binding to sialic-acid receptors, influenza virions are internalized by receptor-mediated endocytosis. The low pH in the endosome triggers the fusion of viral and endosomal membranes, and the influx of H⁺ ions through the M2 channel releases the viral RNA genes in the cytoplasm. Adamantan(amin)e derivatives block this uncoating step. RNA replication and transcription occur in the nucleus. This process can be blocked by inhibitors of inosine 5′-monophosphate (IMP) dehydrogenase (a cellular enzyme) or viral RNA polymerase. The stability of the viral mRNA and its translation to viral protein might be prevented by small interfering RNAs (siRNAs). Packaging and budding of virions occur at the cytoplasmic membrane. Neuraminidase (N) inhibitors block the release of the newly formed virions from the infected cells. Figure adapted with permission from Ref. 8 © (2004) Macmillan Magazines Ltd. H, haemagglutinin.