West Nile Virus envelope glycoprotein (WNV E protein)

The West Nile Virus (WNV) envelope glycoprotein (E protein) is the primary structural protein on the surface of mature virions, where it is organized as 90 antiparallel homodimers. It is a class II viral fusion protein consisting of three distinct domains (DI, DII, and DIII) and is essential for the viral life cycle, mediating both initial attachment to host cell receptors—such as αVβ3 integrin and DC-SIGNR—and subsequent pH-dependent membrane fusion within endosomes [1, 10]. As the principal target of the humoral immune response, the E protein, particularly its immunoglobulin-like domain III (DIII), contains the most potent neutralizing epitopes [2, 6]. Therapeutic strategies targeting this protein include monoclonal antibodies like E16, which block infection by preventing the conformational changes required for fusion, and various vaccine candidates like ChimeriVax-WNV [13, 15]. However, drug development faces significant challenges, including the potential for antibody-dependent enhancement (ADE) due to cross-reactivity with other flaviviruses like Zika and Dengue, as well as the requirement for therapeutics to cross the blood-brain barrier to treat neuroinvasive disease [5, 17, 20].

Other names

WNV EEnvelope protein EGlycoprotein EWest Nile Virus E protein

Neutralization of viral particles, inhibition of viral attachment to host cell receptors, and blockade of pH-dependent membrane fusion by preventing conformational changes of the E protein.