Coxsackievirus A6 capsid proteins VP1–VP4 (CVA6 VP1–VP4)

The Coxsackievirus A6 (CVA6) capsid is an icosahedral structure composed of 60 protomers, each containing four structural proteins: VP1, VP2, VP3, and VP4. VP1, VP2, and VP3 are located on the external surface and form a canyon structure that is critical for host cell recognition, while VP4 is situated on the internal surface of the capsid (PMID: 30382115). These proteins mediate the initial stages of infection by binding to the host cell receptor KREMEN1, which triggers conformational changes leading to the externalization of VP4 and the N-terminus of VP1 to form a pore for genome translocation (PMID: 29681460). CVA6 is a major causative agent of hand, foot, and mouth disease (HFMD) and is increasingly associated with atypical symptoms like eczema coxsackium and severe neurological complications (PMID: 27692044). Because the capsid proteins are the primary targets for the host immune response, they are the focus of vaccine development efforts, including inactivated virus, virus-like particles (VLPs), and subunit vaccines (PMID: 32164101). Experimental antiviral agents, such as capsid-binding inhibitors like pleconaril, aim to stabilize the capsid or block receptor binding to prevent viral entry and uncoating (PMID: 10449211). However, the high rate of genetic recombination and antigenic drift in CVA6 poses significant challenges for long-term therapeutic efficacy and vaccine design.

Other names

CVA6 structural proteinsP1 polyproteinVP1VP2VP3VP4Coxsackievirus A6 capsid

Capsid-binding inhibitors like pleconaril bind to a hydrophobic pocket in the VP1 protein to stabilize the capsid and prevent viral uncoating or receptor binding. Vaccines and neutralizing antibodies target surface-exposed epitopes on VP1, VP2, and VP3 to block attachment to the host cell receptor KREMEN1, thereby preventing viral entry.