Viral protein 1 capsid hydrophobic pocket (VP1 pocket)

The Viral protein 1 (VP1) capsid hydrophobic pocket is a critical regulatory site located within the structural proteins of viruses in the Picornaviridae family, including human rhinoviruses and enteroviruses (Rossmann et al., 1985, Nature). This pocket is typically occupied by a host-derived fatty acid-like molecule called the pocket factor, which maintains the structural integrity of the viral capsid during transmission (Smith et al., 1986, Science). During the infection process, receptor binding triggers the release of this pocket factor, facilitating the conformational shifts required for the virus to uncoat and inject its RNA into the host cytoplasm (Zhang et al., 2008, PNAS). Small molecule inhibitors, known as capsid binders or WIN compounds, are designed to occupy this pocket with high affinity, thereby stabilizing the capsid and blocking the uncoating step (Pevear et al., 1999, Antimicrob. Agents Chemother.). While drugs like Pleconaril and Pocapavir have targeted this site to treat infections like the common cold and neonatal enteroviral sepsis, the high genetic variability of the VP1 region often leads to the rapid development of resistance (Thibaut et al., 2012, Curr. Opin. Virol.). The pocket's accessibility and conserved role in the viral life cycle make it a primary focus for antiviral drug discovery against picornaviruses.

Other names

VP1 hydrophobic pocketVP1 canyonCapsid-binding pocketWIN pocketVP1 hydrophobic cavity

Binding to the VP1 hydrophobic pocket stabilizes the viral capsid, preventing the conformational changes required for viral uncoating and genome release into the host cell (Pevear et al., 1999, Antimicrob. Agents Chemother.).