Functional domains within fusion proteins: Prospectives for development ofpeptide inhibitors of viral cell fusion

The entry of enveloped viruses into host cells is accomplished by fusion of the viral envelope and target plasma membrane and is mediated by fusion pr oteins. Recently, several functional domains within fusion proteins from di fferent viral families were identified. Some are directly involved in confo rmational changes after receptor binding, as suggested by the recent releas e of crystallographically determined structures of a highly stable core str ucture of the fusion proteins in the absence of membranes. However, in the presence of membranes, this core binds strongly to the membrane's surface a nd dissociates therein, Other regions, besides the N-terminal fusion peptid e, which include the core region and an internal fusion peptide in paramyxo viruses, are directly involved in the actual membrane fusion event, suggest ing an "umbrella" like model for the membrane induced conformational change of fusion proteins. Peptides resembling these regions have been shown to h ave specific antiviral activity, presumably because they interfere with the corresponding domains within the viruses. Overall, these studies shed ligh t into the molecular mechanism of membrane fusion induced by envelope glyco proteins and suggest that fusion proteins from different viral families sha re common structural and functional motifs.