Rhinovirus capsid protein (HRV capsid)

The Rhinovirus capsid is the protein shell of the Human Rhinovirus (HRV), the primary cause of the common cold and a major trigger for asthma and COPD exacerbations (PubMed: 17331231). It is composed of 60 protomers, each containing four structural proteins: VP1, VP2, VP3, and VP4, arranged in an icosahedral symmetry (UniProt: P03303). The capsid's primary roles are to protect the viral RNA genome and to facilitate infection by binding to host cell receptors, such as Intercellular Adhesion Molecule 1 (ICAM-1) or the Low-Density Lipoprotein Receptor (LDLR), via a surface feature called the canyon (PubMed: 2544488). Pharmacological targeting of the capsid typically involves small molecules known as capsid binders that fit into a hydrophobic pocket beneath the canyon floor (PubMed: 11911631). These drugs, such as Pleconaril, inhibit viral replication by preventing the conformational changes necessary for the virus to release its genetic material into the host cell (PubChem: CID 104301). Furthermore, these inhibitors can sterically hinder receptor attachment, effectively neutralizing the virus before it enters the cell (PubMed: 10484328). Despite their potential, the clinical utility of capsid binders has been limited by the rapid emergence of drug resistance and the high diversity of HRV serotypes.

Other names

Rhinovirus coat proteinHRV structural proteinCapsid protein VP1Capsid protein VP2Capsid protein VP3Capsid protein VP4VP1VP2VP3VP4

Capsid binders occupy a hydrophobic pocket within the VP1 protein, which either stabilizes the capsid to prevent viral uncoating or induces conformational changes in the canyon floor to block receptor binding (PubMed: 11911631, PubMed: 2544488).