Rhinovirus capsid protein VP1 (VP1) (VP1)

Rhinovirus capsid protein VP1 is the largest and most surface-exposed structural protein of the human rhinovirus (HRV) capsid, which is the primary cause of the common cold and a major trigger for asthma and COPD exacerbations [1, 12]. VP1, along with VP2 and VP3, forms the icosahedral shell of the virus and contains a surface depression known as the "canyon" that serves as the binding site for host cell receptors like ICAM-1 [6, 13]. A key feature of VP1 is a conserved internal hydrophobic pocket that typically contains a host-derived "pocket factor" to maintain capsid stability [7, 15]. This pocket is the primary target for capsid-binding antiviral drugs, such as pleconaril and pirodavir, which displace the pocket factor to either stabilize the capsid against uncoating or block receptor attachment [1, 5, 11]. Despite its potential as a therapeutic target, the high sequence variability of VP1 across more than 160 HRV serotypes poses significant challenges for the development of broad-spectrum antivirals and vaccines [1, 13, 15].

Other names

Viral protein 1HRV VP1Rhinovirus coat protein VP1Capsid protein VP1Major surface protein of the virus capsid

Capsid-binding compounds integrate into a hydrophobic pocket within the VP1 protein, displacing the natural pocket factor. This interaction stabilizes the viral capsid, preventing the conformational changes required for the release (uncoating) of the viral RNA genome into the host cell. Additionally, for some serotypes, drug binding sterically inhibits the attachment of the virus to its cellular receptors, such as ICAM-1.