Viral entry and fusion protein complex

Viral entry and fusion protein complexes are multi-component molecular machineries located on the surface of enveloped viruses that mediate the critical first steps of infection: host cell recognition and membrane fusion (White et al., 2008). These complexes, often composed of glycoproteins, undergo dramatic structural rearrangements triggered by receptor binding or environmental cues like pH changes to merge the viral envelope with the host cell membrane (Harrison, 2015). They are broadly classified into three structural classes (Class I, II, and III), with Class I including well-known targets like the HIV-1 envelope (Env) protein and the Influenza hemagglutinin (HA) (Jackson et al., 2022). As these proteins are essential for viral infectivity and are exposed to the extracellular environment, they serve as primary targets for both the host immune response and therapeutic intervention (Wilen et al., 2012). Pharmacological agents targeting these complexes include attachment inhibitors, co-receptor antagonists, and fusion inhibitors, which prevent the viral genome from entering the host cytoplasm (Stegmann, 2000). While highly effective, drugs targeting these complexes often face challenges such as the rapid development of viral resistance and the need for high specificity to avoid interfering with host cellular processes (Connors et al., 2015). This entry describes a broad class of viral proteins rather than a single molecular target, reflecting the diverse strategies viruses use to breach host barriers.

Other names

Viral fusion machineryViral entry proteinsViral fusion proteinsClass I fusion proteinsClass II fusion proteinsClass III fusion proteinsViral attachment proteins

Inhibition of viral attachment to host cell receptors, antagonism of host cell co-receptors, and inhibition of viral-host membrane fusion by blocking conformational changes in fusion proteins (Stegmann, 2000; Wilen et al., 2012).