Picornaviral capsid protein VP1 (VP1)

The Picornaviral capsid protein VP1 is a primary structural protein that forms the icosahedral shell of viruses within the Picornaviridae family, such as Rhinovirus, Enterovirus, and Poliovirus (UniProt: P03303). It is essential for viral pathogenesis, as it mediates host cell receptor recognition and the subsequent entry of the virus into the cell (PubMed: 2643595). VP1 contains a conserved hydrophobic pocket that naturally accommodates "pocket factors" (typically fatty acids), which regulate the stability of the viral particle (PubMed: 11742400). This pocket is a well-validated therapeutic target for small-molecule antivirals called capsid binders, such as pleconaril and pocapavir, which displace the natural pocket factor to over-stabilize the capsid or block receptor binding (PubMed: 15105405). By preventing the conformational changes necessary for viral uncoating, these drugs effectively halt the release of the viral genome into the host cytoplasm (PubMed: 17110217). However, the clinical utility of targeting VP1 is often challenged by the rapid emergence of resistance mutations within the binding pocket and the high degree of sequence diversity among different picornavirus serotypes.

Other names

Viral protein 1VP1 structural proteinPicornavirus VP1Capsid protein VP1

Capsid stabilization and inhibition of viral uncoating through binding to a hydrophobic pocket within the VP1 protein.