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Enterovirus A71 (EV-A71) capsid protein VP3 is a major structural component of the viral icosahedral shell, essential for maintaining particle integrity and facilitating host cell entry (Plevka et al., 2012, Nature Structural & Molecular Biology). The BC loop and the knob region of VP3 are prominent surface-exposed loops that contribute to the structural landscape of the viral capsid and serve as critical neutralizing epitopes (Plevka et al., 2012). While the primary receptor SCARB2 interacts with multiple capsid proteins, the VP3 regions are essential for the overall stability and the conformational changes required for genome release (Zhou et al., 2019, Nature Communications). Monoclonal antibodies such as D5 and 1H2 specifically target the VP3 knob region, effectively neutralizing the virus by preventing attachment or inhibiting the uncoating process (Wang et al., 2012, Nature Structural & Molecular Biology). In clinical contexts, EV-A71 is the primary causative agent of Hand, Foot, and Mouth Disease (HFMD), which can progress to severe neurological complications such as encephalitis and acute flaccid paralysis (Solomon et al., 2010, Lancet Infectious Diseases). Because the VP3 BC loop and knob are highly conserved among various EV-A71 genotypes, they are prime targets for the development of broad-spectrum vaccines and therapeutic antibodies. However, the potential for antigenic drift and the theoretical risk of antibody-dependent enhancement (ADE) remain significant challenges in targeting these viral surfaces (Zhang et al., 2014, Journal of Virology).
Neutralization of viral infectivity by blocking receptor binding or preventing viral uncoating.
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