Human rhinovirus 16 capsid protein VP1 (HRV16 VP1) (HRV16 VP1)

Human rhinovirus 16 (HRV16) capsid protein VP1 is a major structural protein that forms the icosahedral shell of the virus and contains a specialized hydrophobic pocket located beneath the "canyon" floor (UniProt P09410). This pocket is a critical regulatory site that normally binds a host-derived "pocket factor," typically a fatty acid, which maintains the structural integrity of the virion (PubMed: 11907224). During infection, the displacement of this factor is a prerequisite for the conformational shifts that allow the virus to uncoat and release its genomic RNA into the host cytoplasm (PubMed: 10481563). The VP1 pocket is a well-validated therapeutic target for "capsid binders" such as Pleconaril, which occupy the space to stabilize the capsid and prevent uncoating (PubChem CID 104314). Additionally, drug binding in this pocket can cause a conformational bulge in the canyon floor, potentially interfering with the virus's ability to bind to its primary receptor, Intercellular Adhesion Molecule 1 (ICAM-1) (PubMed: 15680415). Despite its potential, the high mutation rate of the VP1 pocket often leads to the rapid emergence of drug-resistant viral variants (PubMed: 12163546).

Other names

Viral protein 1VP1 hydrophobic pocketCanyon floor pocketCapsid protein VP1HRV16 VP1 pocket

Capsid binders occupy the VP1 hydrophobic pocket, displacing the natural pocket factor and increasing the rigidity of the viral capsid. This stabilization prevents the pH-dependent conformational changes required for viral uncoating and RNA release into the host cell (PubMed: 11907224, 10481563). In some instances, drug binding also induces structural changes in the viral canyon that inhibit attachment to the host receptor ICAM-1 (PubMed: 15680415).