Varicella-Zoster Virus portal protein (ORF54) (ORF54)

The Varicella-Zoster Virus (VZV) portal protein, encoded by ORF54, is an essential component of the viral DNA packaging machinery (UniProt: P09295). It assembles into a dodecameric ring-shaped structure at a single vertex of the icosahedral capsid, serving as the gateway for the entry and exit of the viral genome (PubMed: 15141011). During the replication cycle, ORF54 facilitates the translocation of concatemeric viral DNA into preformed procapsids, a process driven by the viral terminase complex (PubMed: 21680513). Because this packaging mechanism is vital for the production of infectious progeny, ORF54 is a high-priority target for the development of novel antiviral therapies (PubMed: 12885881). Unlike current standard-of-care treatments such as acyclovir, which inhibit the viral DNA polymerase, targeting the portal protein provides a distinct mechanism of action that could be effective against drug-resistant VZV strains (PubMed: 25122779). The absence of a human homolog for this protein minimizes the risk of off-target effects, making it an attractive candidate for drug design. Therapeutic intervention at this stage would prevent the formation of mature virions, thereby mitigating the clinical manifestations of chickenpox and shingles.

Other names

Portal proteinGene 54 proteinp54UL6 homolog

Inhibition of viral DNA encapsidation by blocking the portal through which the viral genome enters the procapsid.