Flavivirus envelope protein (E protein) (E protein)

The Flavivirus envelope protein (E protein) is the primary structural component on the surface of flaviviruses, including Dengue, Zika, and West Nile viruses (PMID: 35412141). It is a class II fusion protein that mediates both the initial attachment of the virus to host cell receptors and the subsequent fusion of the viral and endosomal membranes (PMID: 18602144). On the mature virion, the E protein exists as 90 head-to-tail homodimers arranged in a herringbone pattern (PMC5894644). Upon exposure to the acidic environment of the endosome, the protein undergoes a dramatic conformational change, transitioning from a dimer to a fusogenic trimer that inserts its fusion loop into the host membrane (PMID: 22231303). This process is a critical step in the viral life cycle and is the primary target for neutralizing antibodies and experimental entry inhibitors (PMID: 35412141). Small molecules and peptides targeting the E protein aim to either block receptor binding or stabilize the prefusion dimer to prevent membrane fusion (PMC5894644). However, the high genetic diversity of flaviviruses and the risk of antibody-dependent enhancement (ADE) present significant challenges for therapeutic development (PMID: 18602144).

Other names

Envelope proteinE glycoproteinFlavivirus E proteinViral envelope protein

Inhibition of viral attachment to host receptors and prevention of pH-dependent membrane fusion by stabilizing the prefusion dimer or blocking the fusion loop.