Enterovirus A71 capsid proteins (VP1, VP2, VP3, VP4) (EV-A71 capsid)

Enterovirus A71 (EV-A71) is a significant human pathogen belonging to the Picornaviridae family and is a primary causative agent of hand, foot, and mouth disease (HFMD) (NIH, 2023). The viral capsid is an icosahedral shell composed of 60 protomers, each containing four structural proteins: VP1, VP2, VP3, and VP4 (Frontiers in Microbiology, 2018). VP1, VP2, and VP3 are located on the exterior surface and are responsible for host cell receptor binding to molecules such as SCARB2 and PSGL-1, while VP4 is situated internally and plays a critical role in the uncoating process and genome release (MDPI, 2024). These capsid proteins are major targets for therapeutic intervention, including inactivated vaccines approved in China and small-molecule antiviral agents known as capsid binders (Virology Journal, 2025). Capsid binders typically target a hydrophobic pocket within the VP1 protein, stabilizing the virion to prevent the conformational changes necessary for viral entry and RNA delivery (ACS Infectious Diseases, 2020). Despite the availability of vaccines, the development of effective antivirals is essential for treating severe neurological complications such as encephalitis and acute flaccid paralysis (ResearchGate, 2024). Therapeutic challenges include the rapid emergence of drug-resistant mutations within the capsid genes and the need for broad-spectrum activity across different EV-A71 genotypes (NIH, 2021).

Other names

Enterovirus 71 structural proteinsEV-A71 capsid proteinsP1 polyproteinVP1-VP4 complex

Capsid binding and stabilization: Small molecules bind to the hydrophobic pocket in VP1, displacing the natural pocket factor and preventing the conformational changes required for uncoating and RNA release. Attachment inhibition: Antibodies and certain peptides block the interaction between surface-exposed capsid proteins (primarily VP1) and host cell receptors such as SCARB2 and PSGL-1.