Coxsackievirus A16 capsid proteins VP1–VP4 (CVA16 VP1–VP4)

Coxsackievirus A16 (CVA16) capsid proteins VP1, VP2, VP3, and VP4 are the structural building blocks of the viral icosahedral shell, which protects the positive-sense RNA genome (Chong et al., 2012). These four proteins are derived from the cleavage of the P1 precursor polyprotein and assemble into 60 units, with VP1, VP2, and VP3 located on the exterior and VP4 situated internally (Ren et al., 2015). The surface-exposed proteins form a "canyon" structure that is essential for binding to host cell receptors such as SCARB2 and PSGL-1 (Lin et al., 2018). CVA16 is a major cause of hand, foot, and mouth disease (HFMD), a common childhood illness that can occasionally progress to severe neurological or systemic complications (MicrobeNotes, 2026). The capsid is a primary target for antiviral development, particularly through small-molecule "capsid binders" like GPP3, NLD, and ALD, which occupy a hydrophobic pocket in VP1 to prevent viral uncoating (Ren et al., 2015; MDPI, 2024). These proteins also serve as the main antigens for vaccine candidates, including inactivated viruses and virus-like particles (Chong et al., 2012). However, the high rate of mutation in the capsid genes can lead to the emergence of new subgenotypes and drug-resistant variants, complicating therapeutic and preventative efforts (MDPI, 2025).

Other names

CVA16 structural proteinsCVA16 P1 polyproteinCoxsackievirus A16 VP1, VP2, VP3, and VP4CVA16 capsid

Capsid binders interact with a hydrophobic pocket in the VP1 protein, stabilizing the virion and preventing the conformational changes and uncoating required for genome release (Ren et al., 2015). Other inhibitors, such as tannins, target the canyon region to block receptor binding and viral entry (Lin et al., 2018).