Enveloped virus fusion protein (VFP) (VFP)

Enveloped virus fusion proteins are specialized surface glycoproteins that mediate the critical first steps of viral infection: attachment to host cell receptors and the subsequent fusion of the viral envelope with the host cell membrane (Harrison, S. C., 2008, Nature Reviews Microbiology). These proteins are categorized into three structural classes (I, II, and III) based on their fold and mechanism of action, with examples including the HIV-1 gp120/gp41 complex, the Influenza Hemagglutinin, and the SARS-CoV-2 Spike protein (White, J. M., et al., 2008, Critical Reviews in Biochemistry and Molecular Biology). Upon triggering by specific stimuli such as low pH or receptor binding, these proteins undergo dramatic irreversible conformational changes that pull the viral and cellular membranes into close proximity, facilitating pore formation and genome entry (Kielian, M., 2014, Virology). Because they are essential for the viral life cycle and are exposed on the virion surface, they are primary targets for neutralizing antibodies and small-molecule or peptide-based fusion inhibitors (Bar-Zeev, N., et al., 2021, The Lancet). Therapeutic strategies often focus on stabilizing the pre-fusion state or physically blocking the interaction between the viral protein and its cellular receptor to prevent infection (Eggink, D., et al., 2010, Current Pharmaceutical Design).

Other names

Viral entry machineryViral fusion machineryViral envelope glycoproteinSpike proteinFusion proteinEnvelope protein

Drugs targeting the enveloped virus fusion machinery function by binding to viral surface glycoproteins to prevent the conformational changes required for membrane fusion or by sterically hindering the interaction between the viral protein and its host cell receptor (Eggink, D., et al., 2010, Current Pharmaceutical Design). Peptide-based inhibitors, such as Enfuvirtide, mimic specific regions of the fusion protein to block the formation of the six-helix bundle required for membrane apposition (Wild, C. T., et al., 1994, PNAS). Monoclonal antibodies neutralize the virus by binding to epitopes like the receptor-binding domain or the fusion loop, effectively preventing attachment or the subsequent fusion process (Walker, L. M., & Burton, D. R., 2012, Current Opinion in Immunology).