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Capsid protein VP1 is a primary structural component of the Poliovirus type 3 (Sabin strain) virion, forming the vertices of its icosahedral shell (UniProt: P03301). It is essential for the initial stages of infection, as it mediates binding to the host cell receptor CD155 (PVR) and undergoes significant conformational shifts to facilitate the translocation of the viral genome across the host membrane (PubMed: 1.3.1, 1.5.1). In the context of the Sabin vaccine, VP1 is a key antigenic target for the induction of neutralizing antibodies, but it is also a site of genetic instability where specific mutations can lead to the reversion of the attenuated strain to a neurovirulent phenotype (PubMed: 1.3.2, 1.3.3). Therapeutic strategies targeting VP1 involve small-molecule capsid inhibitors, such as Pocapavir (V-073), which occupy a hydrophobic 'pocket' in the protein, thereby 'locking' the virus in a stable state and blocking the uncoating process necessary for replication (PubMed: 1.1.3, 1.1.4). These inhibitors are particularly relevant for managing chronic infections in immunodeficient individuals and controlling outbreaks associated with vaccine-derived strains (PubMed: 1.1.3).
Capsid inhibitors bind to a hydrophobic pocket within the VP1 protein, which stabilizes the viral capsid and prevents the conformational changes (such as the transition from 160S to 135S particles) required for receptor-mediated uncoating and the subsequent release of the viral RNA genome into the host cell (PubMed: 1.1.2, 1.1.4).
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