Picornaviral capsid protein VP1 hydrophobic pocket (VP1 pocket)

The picornaviral capsid protein VP1 hydrophobic pocket is a critical structural feature found within the icosahedral shell of viruses in the Picornaviridae family, including rhinoviruses and enteroviruses. This pocket is typically located beneath the floor of a surface depression known as the canyon and is naturally occupied by a fatty acid-like molecule called the pocket factor, which regulates the stability of the viral particle [1][2]. During the infection process, the expulsion of this pocket factor is often a prerequisite for the conformational shifts that lead to viral uncoating and genome release [3]. Therapeutic agents, often referred to as capsid binders or WIN compounds, are designed to occupy this pocket with higher affinity than the natural factor [4]. By filling this cavity, these drugs over-stabilize the capsid, effectively locking it in a state that prevents the release of viral RNA into the host cell cytoplasm [5]. Additionally, drug binding can cause the canyon floor to bulge, potentially interfering with the virus's ability to bind to host cell receptors like ICAM-1 or CD155 [6].

Other names

VP1 hydrophobic cavityWIN pocketCapsid-binding pocketVP1 canyon pocket

Binding to the hydrophobic pocket stabilizes the viral capsid, preventing the conformational changes required for the release of the viral RNA genome (uncoating) into the host cell. In some cases, drug binding also induces conformational changes in the nearby canyon region, which can sterically hinder the virus from attaching to its cellular receptors.