Enterovirus D68 P1 polyprotein (P1)

The Enterovirus D68 (EV-D68) P1 polyprotein is the precursor for the structural proteins (VP1, VP2, VP3, and VP4) that assemble to form the viral capsid (UniProt: A0A075I070). During the viral life cycle, the P1 polyprotein is cleaved by the viral 3C protease into individual subunits that organize into an icosahedral shell, which protects the viral RNA genome and facilitates host cell recognition (PubMed: 25554783). EV-D68 is a significant respiratory pathogen that has been increasingly linked to outbreaks of acute flaccid myelitis (AFM), a serious condition characterized by sudden limb weakness and permanent paralysis (CDC). The P1 polyprotein, specifically the VP1 subunit, contains a hydrophobic pocket that is a major target for small-molecule antiviral drugs known as capsid inhibitors, such as pleconaril and pocapavir (PubMed: 26116709). These drugs function by binding within the pocket, thereby stabilizing the capsid and preventing the conformational changes necessary for the virus to release its genome into the host cell (PubMed: 25554783). Furthermore, the P1 polyprotein is the primary target for the development of neutralizing antibodies and vaccines, as it constitutes the outer surface of the infectious virion.

Other names

Capsid protein P1Structural polyprotein P1EV-D68 P1 precursorP1 structural precursor

Capsid stabilization and inhibition of viral uncoating by binding to the hydrophobic pocket of the VP1 subunit.